Project acronym 2D-CHEM
Project Two-Dimensional Chemistry towards New Graphene Derivatives
Researcher (PI) Michal Otyepka
Host Institution (HI) UNIVERZITA PALACKEHO V OLOMOUCI
Country Czechia
Call Details Consolidator Grant (CoG), PE5, ERC-2015-CoG
Summary The suite of graphene’s unique properties and applications can be enormously enhanced by its functionalization. As non-covalently functionalized graphenes do not target all graphene’s properties and may suffer from limited stability, covalent functionalization represents a promising way for controlling graphene’s properties. To date, only a few well-defined graphene derivatives have been introduced. Among them, fluorographene (FG) stands out as a prominent member because of its easy synthesis and high stability. Being a perfluorinated hydrocarbon, FG was believed to be as unreactive as the two-dimensional counterpart perfluoropolyethylene (Teflon®). However, our recent experiments showed that FG is not chemically inert and can be used as a viable precursor for synthesizing graphene derivatives. This surprising behavior indicates that common textbook grade knowledge cannot blindly be applied to the chemistry of 2D materials. Further, there might be specific rules behind the chemistry of 2D materials, forming a new chemical discipline we tentatively call 2D chemistry. The main aim of the project is to explore, identify and apply the rules of 2D chemistry starting from FG. Using the knowledge gained of 2D chemistry, we will attempt to control the chemistry of various 2D materials aimed at preparing stable graphene derivatives with designed properties, e.g., 1-3 eV band gap, fluorescent properties, sustainable magnetic ordering and dispersability in polar media. The new graphene derivatives will be applied in sensing, imaging, magnetic delivery and catalysis and new emerging applications arising from the synergistic phenomena are expected. We envisage that new applications will be opened up that benefit from the 2D scaffold and tailored properties of the synthesized derivatives. The derivatives will be used for the synthesis of 3D hybrid materials by covalent linking of the 2D sheets joined with other organic and inorganic molecules, nanomaterials or biomacromolecules.
Summary
The suite of graphene’s unique properties and applications can be enormously enhanced by its functionalization. As non-covalently functionalized graphenes do not target all graphene’s properties and may suffer from limited stability, covalent functionalization represents a promising way for controlling graphene’s properties. To date, only a few well-defined graphene derivatives have been introduced. Among them, fluorographene (FG) stands out as a prominent member because of its easy synthesis and high stability. Being a perfluorinated hydrocarbon, FG was believed to be as unreactive as the two-dimensional counterpart perfluoropolyethylene (Teflon®). However, our recent experiments showed that FG is not chemically inert and can be used as a viable precursor for synthesizing graphene derivatives. This surprising behavior indicates that common textbook grade knowledge cannot blindly be applied to the chemistry of 2D materials. Further, there might be specific rules behind the chemistry of 2D materials, forming a new chemical discipline we tentatively call 2D chemistry. The main aim of the project is to explore, identify and apply the rules of 2D chemistry starting from FG. Using the knowledge gained of 2D chemistry, we will attempt to control the chemistry of various 2D materials aimed at preparing stable graphene derivatives with designed properties, e.g., 1-3 eV band gap, fluorescent properties, sustainable magnetic ordering and dispersability in polar media. The new graphene derivatives will be applied in sensing, imaging, magnetic delivery and catalysis and new emerging applications arising from the synergistic phenomena are expected. We envisage that new applications will be opened up that benefit from the 2D scaffold and tailored properties of the synthesized derivatives. The derivatives will be used for the synthesis of 3D hybrid materials by covalent linking of the 2D sheets joined with other organic and inorganic molecules, nanomaterials or biomacromolecules.
Max ERC Funding
1 831 103 €
Duration
Start date: 2016-06-01, End date: 2022-05-31
Project acronym ABIONYS
Project Artificial Enzyme Modules as Tools in a Tailor-made Biosynthesis
Researcher (PI) Jan DESKA
Host Institution (HI) AALTO KORKEAKOULUSAATIO SR
Country Finland
Call Details Consolidator Grant (CoG), PE5, ERC-2019-COG
Summary In order to tackle some of the prime societal challenges of this century, science has to urgently provide effective tools addressing the redesign of chemical value chains through the exploitation of novel, bio-based raw materials, and the discovery and implementation of more resource-efficient production platforms. Nature will inevitably play a pivotal role in the imminent transformation of industrial strategies, and the recent bioeconomy approaches can only be regarded as initial step towards a sustainable future. Operating at the interface between chemistry and life sciences, my ABIONYS will fundamentally challenge the widely held distinction separating chemical from biosynthesis, and will deliver the first proof-of-concept where abiotic reactions act as productive puzzle pieces in biosynthetic arrangements. On the basis of our previous ground-breaking discoveries on artificial enzyme functions, I will create a significantly extended toolbox of biocatalysis modules by applying protein-based interpretations of synthetically crucial but non-natural reactions i.e. transformations that are in no way biosynthetically encoded in living organisms. My research will exploit these tools in multi-enzyme cascades for the preparation of complex organic target structures, not only to highlight the great synthetic potential of these approaches, but also to lay the groundwork for in vivo implementations. Eventually, the knowledge gathered from enzyme discovery and cascade design will enable to create an unprecedented class of bioproduction systems, where the genetic incorporation of artificial enzyme functions into recombinant microbial host organisms will yield tailor-made cellular factories. Combining classical organic synthesis strategies with the power of modern biotechnology, ABIONYS is going to transform the way we synthesize complex and functional building blocks by allowing us to encode organic chemistry thinking into living production platforms.
Summary
In order to tackle some of the prime societal challenges of this century, science has to urgently provide effective tools addressing the redesign of chemical value chains through the exploitation of novel, bio-based raw materials, and the discovery and implementation of more resource-efficient production platforms. Nature will inevitably play a pivotal role in the imminent transformation of industrial strategies, and the recent bioeconomy approaches can only be regarded as initial step towards a sustainable future. Operating at the interface between chemistry and life sciences, my ABIONYS will fundamentally challenge the widely held distinction separating chemical from biosynthesis, and will deliver the first proof-of-concept where abiotic reactions act as productive puzzle pieces in biosynthetic arrangements. On the basis of our previous ground-breaking discoveries on artificial enzyme functions, I will create a significantly extended toolbox of biocatalysis modules by applying protein-based interpretations of synthetically crucial but non-natural reactions i.e. transformations that are in no way biosynthetically encoded in living organisms. My research will exploit these tools in multi-enzyme cascades for the preparation of complex organic target structures, not only to highlight the great synthetic potential of these approaches, but also to lay the groundwork for in vivo implementations. Eventually, the knowledge gathered from enzyme discovery and cascade design will enable to create an unprecedented class of bioproduction systems, where the genetic incorporation of artificial enzyme functions into recombinant microbial host organisms will yield tailor-made cellular factories. Combining classical organic synthesis strategies with the power of modern biotechnology, ABIONYS is going to transform the way we synthesize complex and functional building blocks by allowing us to encode organic chemistry thinking into living production platforms.
Max ERC Funding
1 995 707 €
Duration
Start date: 2020-11-01, End date: 2025-10-31
Project acronym ALDof 2DTMDs
Project Atomic layer deposition of two-dimensional transition metal dichalcogenide nanolayers
Researcher (PI) Ageeth Bol
Host Institution (HI) TECHNISCHE UNIVERSITEIT EINDHOVEN
Country Netherlands
Call Details Consolidator Grant (CoG), PE5, ERC-2014-CoG
Summary Two-dimensional transition metal dichalcogenides (2D-TMDs) are an exciting class of new materials. Their ultrathin body, optical band gap and unusual spin and valley polarization physics make them very promising candidates for a vast new range of (opto-)electronic applications. So far, most experimental work on 2D-TMDs has been performed on exfoliated flakes made by the ‘Scotch tape’ technique. The major next challenge is the large-area synthesis of 2D-TMDs by a technique that ultimately can be used for commercial device fabrication.
Building upon pure 2D-TMDs, even more functionalities can be gained from 2D-TMD alloys and heterostructures. Theoretical work on these derivates reveals exciting new phenomena, but experimentally this field is largely unexplored due to synthesis technique limitations.
The goal of this proposal is to combine atomic layer deposition with plasma chemistry to create a novel surface-controlled, industry-compatible synthesis technique that will make large area 2D-TMDs, 2D-TMD alloys and 2D-TMD heterostructures a reality. This innovative approach will enable systematic layer dependent studies, likely revealing exciting new properties, and provide integration pathways for a multitude of applications.
Atomistic simulations will guide the process development and, together with in- and ex-situ analysis, increase the understanding of the surface chemistry involved. State-of-the-art high resolution transmission electron microscopy will be used to study the alloying process and the formation of heterostructures. Luminescence spectroscopy and electrical characterization will reveal the potential of the synthesized materials for (opto)-electronic applications.
The synergy between the excellent background of the PI in 2D materials for nanoelectronics and the group’s leading expertise in ALD and plasma science is unique and provides an ideal stepping stone to develop the synthesis of large-area 2D-TMDs and derivatives.
Summary
Two-dimensional transition metal dichalcogenides (2D-TMDs) are an exciting class of new materials. Their ultrathin body, optical band gap and unusual spin and valley polarization physics make them very promising candidates for a vast new range of (opto-)electronic applications. So far, most experimental work on 2D-TMDs has been performed on exfoliated flakes made by the ‘Scotch tape’ technique. The major next challenge is the large-area synthesis of 2D-TMDs by a technique that ultimately can be used for commercial device fabrication.
Building upon pure 2D-TMDs, even more functionalities can be gained from 2D-TMD alloys and heterostructures. Theoretical work on these derivates reveals exciting new phenomena, but experimentally this field is largely unexplored due to synthesis technique limitations.
The goal of this proposal is to combine atomic layer deposition with plasma chemistry to create a novel surface-controlled, industry-compatible synthesis technique that will make large area 2D-TMDs, 2D-TMD alloys and 2D-TMD heterostructures a reality. This innovative approach will enable systematic layer dependent studies, likely revealing exciting new properties, and provide integration pathways for a multitude of applications.
Atomistic simulations will guide the process development and, together with in- and ex-situ analysis, increase the understanding of the surface chemistry involved. State-of-the-art high resolution transmission electron microscopy will be used to study the alloying process and the formation of heterostructures. Luminescence spectroscopy and electrical characterization will reveal the potential of the synthesized materials for (opto)-electronic applications.
The synergy between the excellent background of the PI in 2D materials for nanoelectronics and the group’s leading expertise in ALD and plasma science is unique and provides an ideal stepping stone to develop the synthesis of large-area 2D-TMDs and derivatives.
Max ERC Funding
1 968 709 €
Duration
Start date: 2015-08-01, End date: 2020-12-31
Project acronym ALLOWE
Project Highly Reactive Low-valent Aluminium Complexes and their Application in Synthesis and Catalysis
Researcher (PI) Shigeyoshi INOUE
Host Institution (HI) TECHNISCHE UNIVERSITAET MUENCHEN
Country Germany
Call Details Consolidator Grant (CoG), PE5, ERC-2020-COG
Summary This ERC-CoG 2020 proposal, ALLOWE outlines a strategy for the development of low-valent aluminium systems through their synthesis, isolation, and reactivity investigation of neutral, ambiphilic, low-valent aluminium compounds, denoted “alumylenes”. Their dimeric form “dialumenes” featuring an aluminium-aluminium double bond will also be within the scope of the project. These low-valent aluminium species are expected to provide, along with greater understanding of the fundamental behaviour of low-valent aluminium, a varied and deep reactivity profile. These highly reactive compounds will offer a cheap, sustainable and non-toxic alternative to the current transition metal-based industrial chemical processes.
The proposed scheme of work begins with the synthesis of neutral alumylenes and dialumenes, respectively. This will be achieved through the use of donor ligands (i.e. N-heterocyclic carbenes) and substituents with differing electronic and steric properties. With these compounds in hand, the reactivity towards small molecules will be investigated along with development of low-valent aluminium based catalysts. Furthermore, incorporation of transition metals into these aluminium systems will be targeted as these may possess unique and interesting properties.
Established methodologies such as reductive dehalogenation or reductive dehydrohalogenation will provide access to novel low-valent aluminium compounds bearing bulky substituents and donor ligands. The synthetic portion of the work will also be supported by theoretical calculations.
The outcome of ALLOWE will provide (i) in-depth insight and understanding into low-valent aluminium’s bonding nature, particularly emphasis laid on ambiphilic aluminium center (ii) plethora of striking reactivity towards transition metal free stoichiometric and catalytic activation of small molecules, and (iii) various potential applications in aluminium-based material chemistry.
Summary
This ERC-CoG 2020 proposal, ALLOWE outlines a strategy for the development of low-valent aluminium systems through their synthesis, isolation, and reactivity investigation of neutral, ambiphilic, low-valent aluminium compounds, denoted “alumylenes”. Their dimeric form “dialumenes” featuring an aluminium-aluminium double bond will also be within the scope of the project. These low-valent aluminium species are expected to provide, along with greater understanding of the fundamental behaviour of low-valent aluminium, a varied and deep reactivity profile. These highly reactive compounds will offer a cheap, sustainable and non-toxic alternative to the current transition metal-based industrial chemical processes.
The proposed scheme of work begins with the synthesis of neutral alumylenes and dialumenes, respectively. This will be achieved through the use of donor ligands (i.e. N-heterocyclic carbenes) and substituents with differing electronic and steric properties. With these compounds in hand, the reactivity towards small molecules will be investigated along with development of low-valent aluminium based catalysts. Furthermore, incorporation of transition metals into these aluminium systems will be targeted as these may possess unique and interesting properties.
Established methodologies such as reductive dehalogenation or reductive dehydrohalogenation will provide access to novel low-valent aluminium compounds bearing bulky substituents and donor ligands. The synthetic portion of the work will also be supported by theoretical calculations.
The outcome of ALLOWE will provide (i) in-depth insight and understanding into low-valent aluminium’s bonding nature, particularly emphasis laid on ambiphilic aluminium center (ii) plethora of striking reactivity towards transition metal free stoichiometric and catalytic activation of small molecules, and (iii) various potential applications in aluminium-based material chemistry.
Max ERC Funding
1 997 750 €
Duration
Start date: 2021-06-01, End date: 2026-05-31
Project acronym ANFIBIO
Project AmplificatioN Free Identification of cancer and viral biomarkers via plasmonic nanoparticles and liquid BIOpsy
Researcher (PI) Laura Fabris
Host Institution (HI) POLITECNICO DI TORINO
Country Italy
Call Details Consolidator Grant (CoG), PE5, ERC-2019-COG
Summary The detection of circulating disease biomarkers in bodily fluids, also known as liquid biopsy, has taken important strides toward the implementation of personalized medicine. However, it still suffers from low sensitivity and high costs, which render its clinical implementation not practical or affordable. In particular, the identification and quantification of oligonucleotide biomarkers is hampered by the need to employ long- and short-read sequencing tools that are expensive, require highly trained personnel, and are prone to error. Nonetheless, the recent clinical breakthroughs demonstrating the importance of detecting cancerous or viral biomarker to susceptibility, onset, and aggressiveness of the disease, motivate the need for further research that could render their detection simpler, cheaper, and thus more widely available.
By leveraging the intrinsic amplification capability of surface enhanced Raman scattering (SERS), in ANFIBIO I will address the issues of low sensitivity and high costs by combining plasmonic nanoparticles synthesized ad hoc to maximize SERS signal amplification with direct SERS sensing and machine learning tools for the rapid analysis of the complex spectral responses obtained by screening bodily fluids for specific target biomarkers. I will focus in particular on prostate cancer (PCa) DNA and influenza A viral (IAV) RNA in blood, urine, and saliva, to quantify and correlate their amounts to those detected in tissues and cells.
At completion, the proposed work will deliver a breakthrough sensing technology capable of detecting and quantifying cancerous and viral biomarkers in bodily fluids, with minimal sample pretreatment, no target amplification, and that uses SERS as novel and reliable transduction mechanism with distinct advantages over those currently employed. Furthermore, the fundamental insight garnered will likely assess the feasibility of using direct SERS sensing to develop beyond-third generation sequencing technologies.
Summary
The detection of circulating disease biomarkers in bodily fluids, also known as liquid biopsy, has taken important strides toward the implementation of personalized medicine. However, it still suffers from low sensitivity and high costs, which render its clinical implementation not practical or affordable. In particular, the identification and quantification of oligonucleotide biomarkers is hampered by the need to employ long- and short-read sequencing tools that are expensive, require highly trained personnel, and are prone to error. Nonetheless, the recent clinical breakthroughs demonstrating the importance of detecting cancerous or viral biomarker to susceptibility, onset, and aggressiveness of the disease, motivate the need for further research that could render their detection simpler, cheaper, and thus more widely available.
By leveraging the intrinsic amplification capability of surface enhanced Raman scattering (SERS), in ANFIBIO I will address the issues of low sensitivity and high costs by combining plasmonic nanoparticles synthesized ad hoc to maximize SERS signal amplification with direct SERS sensing and machine learning tools for the rapid analysis of the complex spectral responses obtained by screening bodily fluids for specific target biomarkers. I will focus in particular on prostate cancer (PCa) DNA and influenza A viral (IAV) RNA in blood, urine, and saliva, to quantify and correlate their amounts to those detected in tissues and cells.
At completion, the proposed work will deliver a breakthrough sensing technology capable of detecting and quantifying cancerous and viral biomarkers in bodily fluids, with minimal sample pretreatment, no target amplification, and that uses SERS as novel and reliable transduction mechanism with distinct advantages over those currently employed. Furthermore, the fundamental insight garnered will likely assess the feasibility of using direct SERS sensing to develop beyond-third generation sequencing technologies.
Max ERC Funding
2 725 510 €
Duration
Start date: 2021-06-01, End date: 2026-05-31
Project acronym Autocat
Project Autocatalysis: A bottom-up approach to understanding the origins of life
Researcher (PI) Stephen Patrick Fletcher
Host Institution (HI) THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Country United Kingdom
Call Details Consolidator Grant (CoG), PE5, ERC-2015-CoG
Summary "The origin of life is not well understood, and is one of the great remaining questions in science. Autocatalytic chemical reactions have been extensively studied with the aim of providing insight into the principles underlying living systems. In biology, organisms can be thought of as imperfect self-replicators, which produce closely related species, allowing for selection and evolution. Autocatalysis is also an important part of many other biological processes.
This project aims to develop new autocatalytic reactions where two simple chemical building blocks come together to give a more complex product, and then the product aggregates to give primitive cell-like structures or ""protocells"" such as micelles or vesicles. The protocells allow the starting materials to mix more efficiently, speeding up the reaction in time and giving rise to complex behaviour of the protocells. These reactions will serve as models that I hope will contribute to understanding how cell-like systems can emerge from simpler chemicals and be relevant to how life started on earth.
This project will give the opportunity to study chemical systems that may be able to evolve in time, allow development of useful chemical models of important biological processes, and provide ‘bottom-up’ approaches to synthetic biology. This research will potential allow the study evolution in a new ways, develop technology useful to a number of scientific fields, and potentially shed light on the processes that allowed chemistry to become biology on the primitive Earth."
Summary
"The origin of life is not well understood, and is one of the great remaining questions in science. Autocatalytic chemical reactions have been extensively studied with the aim of providing insight into the principles underlying living systems. In biology, organisms can be thought of as imperfect self-replicators, which produce closely related species, allowing for selection and evolution. Autocatalysis is also an important part of many other biological processes.
This project aims to develop new autocatalytic reactions where two simple chemical building blocks come together to give a more complex product, and then the product aggregates to give primitive cell-like structures or ""protocells"" such as micelles or vesicles. The protocells allow the starting materials to mix more efficiently, speeding up the reaction in time and giving rise to complex behaviour of the protocells. These reactions will serve as models that I hope will contribute to understanding how cell-like systems can emerge from simpler chemicals and be relevant to how life started on earth.
This project will give the opportunity to study chemical systems that may be able to evolve in time, allow development of useful chemical models of important biological processes, and provide ‘bottom-up’ approaches to synthetic biology. This research will potential allow the study evolution in a new ways, develop technology useful to a number of scientific fields, and potentially shed light on the processes that allowed chemistry to become biology on the primitive Earth."
Max ERC Funding
2 278 073 €
Duration
Start date: 2016-05-01, End date: 2021-10-31
Project acronym BECAME
Project Bimetallic Catalysis for Diverse Methane Functionalization
Researcher (PI) MartIn FAnANaS-MASTRAL
Host Institution (HI) UNIVERSIDAD DE SANTIAGO DE COMPOSTELA
Country Spain
Call Details Consolidator Grant (CoG), PE5, ERC-2019-COG
Summary One of the remaining primary challenges in modern chemistry is the development of clean, energy- and cost-efficient catalytic processes that can allow to convert simple and abundant chemical feedstocks into high value-added products. Given the vast reserves of methane from natural gas, available worldwide, the direct use of the simplest alkane as source of fuels and chemicals could have a great impact in our society. However, methane´s low intrinsic reactivity has rendered its use extremely difficult for purposes beyond aerobic combustion and the production of syngas. Despite some recent advances in the field, a general strategy for a diverse and versatile use of methane is elusive.
The overall aim of this proposal is the development of a new paradigm in catalysis which can provide new catalytic processes that allow direct methane functionalization by using it as a methylating reagent in a variety of C-C bond forming reactions.
The approach described in this proposal is based on a cooperative interaction between two transition metal complexes in which an early transition metal is responsible for the methane C-H activation and a late transition metal is the actual catalyst of the methylation process. The link between these two processes is a transmetalation step and will be used to transfer the mechanism of typical cross-coupling reactions to the field of methane functionalization.
New pathways for the direct use of methane in reactions such as allylic alkylation, conjugate addition, cross-coupling, C-H methylation and alkene hydromethylation will be developed based on this novel bimetallic catalytic strategy.
It is envisioned that the proposed research will lead to a new concept at the interface of catalytic cross coupling reactions and C-H activation. It will contribute to the fundamental understanding of these two reactions and will provide the basis for a new technology for energy efficient and environmentally friendly, thus sustainable, methane conversion.
Summary
One of the remaining primary challenges in modern chemistry is the development of clean, energy- and cost-efficient catalytic processes that can allow to convert simple and abundant chemical feedstocks into high value-added products. Given the vast reserves of methane from natural gas, available worldwide, the direct use of the simplest alkane as source of fuels and chemicals could have a great impact in our society. However, methane´s low intrinsic reactivity has rendered its use extremely difficult for purposes beyond aerobic combustion and the production of syngas. Despite some recent advances in the field, a general strategy for a diverse and versatile use of methane is elusive.
The overall aim of this proposal is the development of a new paradigm in catalysis which can provide new catalytic processes that allow direct methane functionalization by using it as a methylating reagent in a variety of C-C bond forming reactions.
The approach described in this proposal is based on a cooperative interaction between two transition metal complexes in which an early transition metal is responsible for the methane C-H activation and a late transition metal is the actual catalyst of the methylation process. The link between these two processes is a transmetalation step and will be used to transfer the mechanism of typical cross-coupling reactions to the field of methane functionalization.
New pathways for the direct use of methane in reactions such as allylic alkylation, conjugate addition, cross-coupling, C-H methylation and alkene hydromethylation will be developed based on this novel bimetallic catalytic strategy.
It is envisioned that the proposed research will lead to a new concept at the interface of catalytic cross coupling reactions and C-H activation. It will contribute to the fundamental understanding of these two reactions and will provide the basis for a new technology for energy efficient and environmentally friendly, thus sustainable, methane conversion.
Max ERC Funding
1 999 679 €
Duration
Start date: 2020-09-01, End date: 2025-08-31
Project acronym BENOVELTY
Project Saturated bioisosteres of benzene and their application in drug design
Researcher (PI) Pavlo MYKHAILIUK
Host Institution (HI) ENAMINE LIMITED LIABILITY COMPANY,RESEARCH AND PRODUCTION ENTERPRISE
Country Ukraine
Call Details Consolidator Grant (CoG), PE5, ERC-2020-COG
Summary More than 500 of all existing drugs are phenyl-containing organic molecules. During the recent years, however, pharmaceutical companies struggle to deliver novel drugs to the market, because of the lack of innovative practical approaches towards novel drug-like “chemical space.” In this project, we will address this issue by developing novel saturated bioisosteres for ortho- and meta-substituted benzenes, and incorporate them into several known drugs (intiinflamatory Aceclofenac, antiviral Tipranavir, antihypertensive Oxprenolol, etc) to provide novel patent-free analogues with improved physico-chemical and biological properties.
Summary
More than 500 of all existing drugs are phenyl-containing organic molecules. During the recent years, however, pharmaceutical companies struggle to deliver novel drugs to the market, because of the lack of innovative practical approaches towards novel drug-like “chemical space.” In this project, we will address this issue by developing novel saturated bioisosteres for ortho- and meta-substituted benzenes, and incorporate them into several known drugs (intiinflamatory Aceclofenac, antiviral Tipranavir, antihypertensive Oxprenolol, etc) to provide novel patent-free analogues with improved physico-chemical and biological properties.
Max ERC Funding
1 997 500 €
Duration
Start date: 2021-04-01, End date: 2026-03-31
Project acronym BETACONTROL
Project Control of amyloid formation via beta-hairpin molecular recognition features
Researcher (PI) Wolfgang HOYER
Host Institution (HI) HEINRICH-HEINE-UNIVERSITAET DUESSELDORF
Country Germany
Call Details Consolidator Grant (CoG), PE5, ERC-2016-COG
Summary The aggregation of proteins into amyloid fibrils is involved in various diseases which place a high burden on patients, families, caregivers, and healthcare systems, including Alzheimer’s disease, Parkinson’s disease and type 2 diabetes. While the therapeutic potential of the inhibition of amyloid formation and spreading has been recognized, there is a lack of effective strategies targeting the early steps of the aggregation reaction.
In BETACONTROL, I want to establish a structure-guided approach to the control of amyloid formation and spreading. I will develop small molecule and polypeptide-based ligands that interfere with the initial phases of amyloid formation and thereby suppress any toxic oligomeric or fibrillar assemblies. The ligands will target beta-hairpin molecular recognition features, which I found to be readily accessible in disease-related amyloidogenic proteins. Targeting beta-hairpins enables retardation of protein aggregation by substoichiometric amounts of the ligand, affording inhibition of amyloid formation at low compound concentrations. As the strategy addresses the common propensity of amyloidogenic proteins to adopt beta-structure, it will be applicable to a wide range of proteins associated with various diseases.
BETACONTROL will yield molecular-level insight into the mechanistic basis of amyloid formation and spreading. Furthermore, it will elucidate the significance of beta-hairpins as molecular recognition features in intrinsically disordered proteins (IDPs) and highlight the applicability of these features as targets for interference with protein-protein interactions of IDPs. Ultimately, BETACONTROL will provide a novel therapeutic approach to a range of devastating diseases.
Summary
The aggregation of proteins into amyloid fibrils is involved in various diseases which place a high burden on patients, families, caregivers, and healthcare systems, including Alzheimer’s disease, Parkinson’s disease and type 2 diabetes. While the therapeutic potential of the inhibition of amyloid formation and spreading has been recognized, there is a lack of effective strategies targeting the early steps of the aggregation reaction.
In BETACONTROL, I want to establish a structure-guided approach to the control of amyloid formation and spreading. I will develop small molecule and polypeptide-based ligands that interfere with the initial phases of amyloid formation and thereby suppress any toxic oligomeric or fibrillar assemblies. The ligands will target beta-hairpin molecular recognition features, which I found to be readily accessible in disease-related amyloidogenic proteins. Targeting beta-hairpins enables retardation of protein aggregation by substoichiometric amounts of the ligand, affording inhibition of amyloid formation at low compound concentrations. As the strategy addresses the common propensity of amyloidogenic proteins to adopt beta-structure, it will be applicable to a wide range of proteins associated with various diseases.
BETACONTROL will yield molecular-level insight into the mechanistic basis of amyloid formation and spreading. Furthermore, it will elucidate the significance of beta-hairpins as molecular recognition features in intrinsically disordered proteins (IDPs) and highlight the applicability of these features as targets for interference with protein-protein interactions of IDPs. Ultimately, BETACONTROL will provide a novel therapeutic approach to a range of devastating diseases.
Max ERC Funding
1 920 697 €
Duration
Start date: 2017-06-01, End date: 2022-05-31
Project acronym BIOINOHYB
Project Smart Bioinorganic Hybrids for Nanomedicine
Researcher (PI) Cristiana Di Valentin
Host Institution (HI) UNIVERSITA' DEGLI STUDI DI MILANO-BICOCCA
Country Italy
Call Details Consolidator Grant (CoG), PE5, ERC-2014-CoG
Summary The use of bioinorganic nanohybrids (nanoscaled systems based on an inorganic and a biological component) has already resulted in several innovative medical breakthroughs for drug delivery, therapeutics, imaging, diagnosis and biocompatibility. However, researchers still know relatively little about the structure, function and mechanism of these nanodevices. Theoretical investigations of bioinorganic interfaces are mostly limited to force-field approaches which cannot grasp the details of the physicochemical mechanisms. The BIOINOHYB project proposes to capitalize on recent massively parallelized codes to investigate bioinorganic nanohybrids by advanced quantum chemical methods. This approach will allow to master the chemical and electronic interplay between the bio and the inorganic components in the first part of the project, and the interaction of the hybrid systems with light in the second part. The ultimate goal is to provide the design principles for novel, unconventional assemblies with unprecedented functionalities and strong impact potential in nanomedicine.
More specifically, in this project the traditional metallic nanoparticle will be substituted by emerging semiconducting metal oxide nanostructures with photocatalytic or magnetic properties capable of opening totally new horizons in nanomedicine (e.g. photocatalytic therapy, a new class of contrast agents, magnetically guided drug delivery). Potentially efficient linkers will be screened regarding their ability both to anchor surfaces and to bind biomolecules. Different kinds of biomolecules (from oligopeptides and oligonucleotides to small drugs) will be tethered to the activated surface according to the desired functionality. The key computational challenge, requiring the recourse to more sophisticated methods, will be the investigation of the photo-response to light of the assembled bioinorganic systems, also with specific reference to their labelling with fluorescent markers and contrast agents.
Summary
The use of bioinorganic nanohybrids (nanoscaled systems based on an inorganic and a biological component) has already resulted in several innovative medical breakthroughs for drug delivery, therapeutics, imaging, diagnosis and biocompatibility. However, researchers still know relatively little about the structure, function and mechanism of these nanodevices. Theoretical investigations of bioinorganic interfaces are mostly limited to force-field approaches which cannot grasp the details of the physicochemical mechanisms. The BIOINOHYB project proposes to capitalize on recent massively parallelized codes to investigate bioinorganic nanohybrids by advanced quantum chemical methods. This approach will allow to master the chemical and electronic interplay between the bio and the inorganic components in the first part of the project, and the interaction of the hybrid systems with light in the second part. The ultimate goal is to provide the design principles for novel, unconventional assemblies with unprecedented functionalities and strong impact potential in nanomedicine.
More specifically, in this project the traditional metallic nanoparticle will be substituted by emerging semiconducting metal oxide nanostructures with photocatalytic or magnetic properties capable of opening totally new horizons in nanomedicine (e.g. photocatalytic therapy, a new class of contrast agents, magnetically guided drug delivery). Potentially efficient linkers will be screened regarding their ability both to anchor surfaces and to bind biomolecules. Different kinds of biomolecules (from oligopeptides and oligonucleotides to small drugs) will be tethered to the activated surface according to the desired functionality. The key computational challenge, requiring the recourse to more sophisticated methods, will be the investigation of the photo-response to light of the assembled bioinorganic systems, also with specific reference to their labelling with fluorescent markers and contrast agents.
Max ERC Funding
1 748 125 €
Duration
Start date: 2016-02-01, End date: 2022-07-31
