Development of an Integrated Microfluidic Platform for the Identification of Therapeutic Peptides for Unmet Medical Needs
Lead Research Organisation:
UNIVERSITY OF CAMBRIDGE
Department Name: Chemistry
Abstract
Pharmaceutical industries have recognised the importance of cell-permeable peptides to cure currently untreatable diseases. In fact, peptides can interact with targets that other type of molecules cannot, such as protein-protein interactions which play crucial roles in the generation and progression of many diseases. However, peptides also have major limitations that hamper their use as drugs. Among these is their inability to efficiently interact with intracellular targets leaving many unmet medical needs.
We propose to develop an integrated platform to generate and screen libraries of peptides to rapidly and cost-effectively identify new drugs for those untapped intracellular targets. In the first phase of the proposed research, we will focus our efforts on building such a platform, and in the second phase we will validate it using two different intracellular targets with relevance in cancer and cystic fibrosis.
A successful outcome to this project will result in a significant advance in the drug-discovery field as current peptide technologies can only access extracellular targets, ignoring those 75% located intracellularly. Therefore, our technology has the potential to provide patients with life-changing medicines for currently untreatable diseases or for diseases with limited therapeutic options available.
We propose to develop an integrated platform to generate and screen libraries of peptides to rapidly and cost-effectively identify new drugs for those untapped intracellular targets. In the first phase of the proposed research, we will focus our efforts on building such a platform, and in the second phase we will validate it using two different intracellular targets with relevance in cancer and cystic fibrosis.
A successful outcome to this project will result in a significant advance in the drug-discovery field as current peptide technologies can only access extracellular targets, ignoring those 75% located intracellularly. Therefore, our technology has the potential to provide patients with life-changing medicines for currently untreatable diseases or for diseases with limited therapeutic options available.
Publications

Iegre J
(2023)
A cell-active cyclic peptide targeting the Nrf2/Keap1 protein-protein interaction.
in Chemical science

Kapun M
(2024)
Red-light modulated ortho-chloro azobenzene photoswitch for peptide stapling via aromatic substitution.
in RSC chemical biology

Krajcovicova S
(2023)
Tryptophan in Multicomponent Petasis Reactions for Peptide Stapling and Late-Stage Functionalisation.
in Angewandte Chemie (International ed. in English)

Krajcovicova S
(2023)
Tryptophan in Multicomponent Petasis Reactions for Peptide Stapling and Late-Stage Functionalisation
in Angewandte Chemie


Pantelejevs T
(2023)
A recombinant approach for stapled peptide discovery yields inhibitors of the RAD51 recombinase
in Chemical Science

Walther R
(2023)
Identification of macrocyclic peptides which activate bacterial cylindrical proteases.
in RSC medicinal chemistry

Zenkeviciute G
(2023)
Development of constrained peptide inhibitors targeting an oncogenic E3 ubiquitin ligase
Description | Pharmaceutical industries have recognised the importance of cell-permeable peptides to cure currently untreatable diseases. In fact, peptides can interact with targets that other type of molecules cannot, such as protein-protein interactions which play crucial roles in the generation and progression of many diseases. However, peptides also have major limitations that hamper their use as drugs. Among these is their inability to efficiently interact with intracellular targets leaving many unmet medical needs. We have developed an integrated platform to generate and screen libraries of peptides to rapidly and cost-effectively identify new drugs for those untapped intracellular targets. In the first phase we have been able to build such a platform, and in the second phase we have started to validate it in antibacterial assays. |
Exploitation Route | The platform can be further optimised and validated on other targets. We are looking to secure further funding in order to do this. |
Sectors | Chemicals Healthcare Pharmaceuticals and Medical Biotechnology |
Description | Applied to make macrocyclic peptides that can me used to target cell types. |
First Year Of Impact | 2023 |
Sector | Pharmaceuticals and Medical Biotechnology |
Impact Types | Economic |
Description | Bicyclic Peptides |
Amount | £750,000 (GBP) |
Funding ID | G118186 |
Organisation | Bicycle Therapeutics |
Sector | Private |
Country | United Kingdom |
Start | 08/2023 |
End | 08/2024 |
Description | Bicycle TX Collaboration |
Organisation | Bicycle Therapeutics |
Country | United Kingdom |
Sector | Private |
PI Contribution | We are collaborating on new macrocyclic peptides and modes of action. |
Collaborator Contribution | Testing of macrocyclic peptides and commercialisation. |
Impact | The aim is to commercialise this research, so we have not published results yet. |
Start Year | 2022 |