Synthetic Methods for Conversion of Linear Peptides into Peptide Macrocycles
Lead Research Organisation:
University of Cambridge
Department Name: Chemistry
Abstract
This project describes the development of a method to turn native linear peptides into non-natural macrocyclic ligands. Based on reactions at site-specific peptide conjugates, a catalyst will enable linkage to tryptophan, tyrosine and histidine amino acids residues, resulting in the peptide macrocycles. These new macrocyclic molecules can be used to probe protein-protein interactions in disease-related systems.
Organisations
People |
ORCID iD |
| Matthew Gaunt (Primary Supervisor) | |
| Patrick Deneny (Student) |
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| EP/N509620/1 | 01/10/2016 | 30/09/2022 | |||
| 1942975 | Studentship | EP/N509620/1 | 01/10/2017 | 30/09/2021 | Patrick Deneny |
| Description | Peptide macrocycles are an attractive class of compounds due to their potential value as novel therapeutics to treat traditionally 'undruggable' diseases. As a result of the work funded through this award, a novel method for the synthesis of peptide macrocycles directly from native peptides has been developed. This method is rapid and highly efficient, providing access to novel peptide macrocycles that are potentially valuable lead compounds in the development of new disease treatments. |
| Exploitation Route | The scope of the method towards a wider variety of peptides and cyclization strategies could be explored. The biological properties of the peptide macrocycle products could be explored and their value as drug leads investigated in either an academic or industrial setting. |
| Sectors | Chemicals,Pharmaceuticals and Medical Biotechnology |
| Title | Novel synthetic method for the conversion of linear peptides into peptide macrocycles |
| Description | A novel synthetic method for the conversion of linear peptides into peptide macrocycles has been developed. This method comprises three highly efficient and rapid synthetic steps, without purification being required between each step (a 'three-step, one-pot' procedure). In the first step, two different natural amino acid residues are simultaneously and selectively labelled using two distinct reagents that bear complementary functionality for use in the final macrocyclization step (an azide and an alkyne, respectively). The second step is a selective and mild reduction of one of the labels to enhance its stability. The third step is a copper(I)-catalyzed azide alkyne cycloaddition (CuAAC) 'click' reaction between the two complementary labels to form the peptide macrocycle product. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2020 |
| Provided To Others? | No |
| Impact | This method provides rapid and facile access to peptide macrocycles directly from native peptide sequences. In comparison with existing methods, it is a simple and efficient strategy for the synthesis of macrocyclic peptides which are potentially valuable products for the development of novel therapeutics. |
| Description | Poster presentation during Chemistry Showcase Week (University of Cambridge) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Postgraduate students |
| Results and Impact | I presented my current research in the form of a poster to other postgraduate students and postdoctoral researchers as part of the annual Chemistry Showcase Week. Students from other research groups were made aware of the work, which sparked questions and discussion during the poster session. |
| Year(s) Of Engagement Activity | 2019 |