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

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posted on 2023-07-26, 14:19 authored by Jessica Iegre, Niaz S. Ahmed, Josephine S. Gaynord, Yuteng Wu, Kara M. Herlihy, Yaw Sing Tan, Maria E. Lopes-Pires, Rupam Jha, Yu Heng Lau, Hannah F. Sore, Chandra Verma, Daniel H. O'Donovan, Nicholas Pugh, David R. Spring
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 coventional 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.

History

Refereed

  • Yes

Volume

9

Issue number

20

Page range

4638-4643

Publication title

Chemical Science

ISSN

2041-6539

Publisher

Royal Society of Chemistry

File version

  • Published version

Language

  • eng

Legacy posted date

2018-04-26

Legacy creation date

2018-04-25

Legacy Faculty/School/Department

ARCHIVED Faculty of Science & Technology (until September 2018)

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