Issue 20, 2018

Stapled peptides as a new technology to investigate protein–protein interactions in human platelets

Abstract

Platelets are blood cells with numerous crucial pathophysiological roles in hemostasis, cardiovascular thrombotic events and cancer metastasis. Platelet activation requires the engagement of intracellular signalling pathways that involve protein–protein interactions (PPIs). A better understanding of these pathways is therefore crucial for the development of selective anti-platelet drugs. New strategies for studying PPIs in human platelets are required to overcome limitations associated with conventional platelet research methods. For example, small molecule inhibitors can lack selectivity and are often difficult to design and synthesise. Additionally, development of transgenic animal models is costly and time-consuming and conventional recombinant techniques are ineffective due to the lack of a nucleus in platelets. Herein, we describe the generation of a library of novel, functionalised stapled peptides and their first application in the investigation of platelet PPIs. Moreover, the use of platelet-permeable stapled Bim BH3 peptides confirms the part of Bim in phosphatidyl-serine (PS) exposure and reveals a role for the Bim protein in platelet activatory processes. Our work demonstrates that functionalised stapled peptides are a complementary alternative to conventional platelet research methods, and could make a significant contribution to the understanding of platelet signalling pathways and hence to the development of anti-platelet drugs.

Graphical abstract: Stapled peptides as a new technology to investigate protein–protein interactions in human platelets

Supplementary files

Article information

Article type
Edge Article
Submitted
18 jan 2018
Accepted
23 abr 2018
First published
25 abr 2018
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2018,9, 4638-4643

Stapled peptides as a new technology to investigate protein–protein interactions in human platelets

J. Iegre, N. S. Ahmed, J. S. Gaynord, Y. Wu, K. M. Herlihy, Y. S. Tan, M. E. Lopes-Pires, R. Jha, Y. H. Lau, H. F. Sore, C. Verma, D. H. O' Donovan, N. Pugh and D. R. Spring, Chem. Sci., 2018, 9, 4638 DOI: 10.1039/C8SC00284C

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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