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Title: Stapled peptides as a new technology to investigate protein–protein interactions in human platelets
Authors: Iegre, Jessica
Ahmed, Niaz S.
Gaynord, Josephine S.
Wu, Yuteng
Herlihy, Kara M.
Tan, Yaw Sing
Lopes-Pires, Maria E.
Jha, Rupam
Lau, Yu Heng
Sore, Hannah F.
Verma, Chandra
O' Donovan, Daniel H.
Pugh, Nicholas
Spring, David R.
Keywords: Platelets
Stapled Peptides
Issue Date: 2018
Source: Iegre, J., Ahmed, N. S., Gaynord, J. S., Wu, Y., Herlihy, K. M., Tan, Y. S., et al. (2018). Stapled peptides as a new technology to investigate protein–protein interactions in human platelets. Chemical Science, 9(20), 4638-4643.
Series/Report no.: Chemical Science
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.
ISSN: 2041-6520
Rights: © 2018 The Author(s) (published by Royal Society of Chemistry). This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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