Objective
Many critical processes within cells, including those that control whether a cell lives and divides or dies, are mediated by protein–protein interactions (PPIs). In certain disease states, such as cancer, these interactions can become defective in a way where disruption of the interaction has therapeutic benefit. Replacement of one of the protein partners, which often have α-helical secondary structure, with a small molecule is one method of disruption; however, the interface can often be large and shallow, making the design of competitive small molecules challenging. The saving grace is that the interaction energy is usually dominated by the interactions of a few amino acid residues, which protrude from one or more faces of the α-helical peptide. The design of α-helical mimetics that are non-peptidic in nature and that can replicate the positioning of these hotspot residues has been an active area of research. The host laboratory has recently developed a method to prepare chains of substituted carbon atoms with complete control of absolute and relative configuration. Owing to the avoidance of syn-pentane interactions, the all-syn and alternating syn–anti contiguously substituted chains fold into well-defined helical and linear conformations. The positioning of the substituents could uniquely replicate a pattern of hotspot residues that cover two or more faces of an α-helical peptide. This project will explore this possibility through the design, preparation and testing of mimetics that target the Mcl-1/Noxa-B PPI, which controls apoptosis and has leucine, arginine, isoleucine, aspartic acid, and valine at positions 11, 12, 14, 16 and 18 as hotspot residues. The project merges cutting-edge synthetic organic chemistry, multiple forms of computation, including molecular mechanics, density functional theory, and molecular dynamics, NMR spectroscopy, and medicinal chemistry.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences basic medicine medicinal chemistry
- natural sciences chemical sciences organic chemistry hydrocarbons
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences physical sciences optics spectroscopy absorption spectroscopy
- natural sciences chemical sciences organic chemistry amines
You need to log in or register to use this function
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
-
H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
See all projects funded under this programme -
H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
See all projects funded under this programme
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
MSCA-IF-EF-ST - Standard EF
See all projects funded under this funding scheme
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2017
See all projects funded under this callCoordinator
Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
BS8 1QU BRISTOL
United Kingdom
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.