Issue 9, 2020
From the journal:

RSC Medicinal Chemistry

Synthesis and biological evaluation of S-lipidated lipopeptides of a connexin 43 channel inhibitory peptide†

Sung-Hyun Yang,‡ab   Connor A. Clemett,‡c   Margaret A. Brimble, ORCID logo abd   Simon J. O'Carroll*c  and  Paul W. R. Harris ORCID logo *abd  

* Corresponding authors

a School of Chemical Sciences, The University of Auckland, 23 Symonds St, Auckland, New Zealand
E-mail: paul.harris@auckland.ac.nz

b School of Biological Sciences, The University of Auckland, 3a Symonds St, Private Bag 92019, Auckland, New Zealand

c Department of Anatomy Medical Imaging, School of Medical Sciences, Faculty of Medical and Health Sciences, and Centre for Brain Research, University of Auckland, Private Bag 92019, Auckland, New Zealand
E-mail: s.ocarroll@auckland.ac.nz

d Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, 3a Symonds St, Auckland, New Zealand

Abstract

The synthesis and biological activity of 42 novel S-lipidated analogues of a connexin 43 channel inhibitory Peptide5 is described. Unmodified Peptide5 moderates hemichannels and gap junctions that are both implicated in the progression of neurological disease. Peptide5 was site-specifically modified with a cysteine residue, which then underwent thiol–ene mediated S-lipidation to afford S-lipidated Peptide5 analogues containing straight-chain, branched, or aromatic lipids. The modified peptides were assessed for their effect on hemichannel opening and the most promising candidates were evaluated in serum stability studies.

Graphical abstract: Synthesis and biological evaluation of S-lipidated lipopeptides of a connexin 43 channel inhibitory peptide

About
Cited by
Related
Download options Please wait...

Supplementary files

Article information

DOI
https://doi.org/10.1039/D0MD00172D
Article type
Research Article
Submitted
25 May 2020
Accepted
18 Jun 2020
First published
10 Jul 2020

RSC Med. Chem., 2020,11, 1041-1047

Permissions

Request permissions

Synthesis and biological evaluation of S-lipidated lipopeptides of a connexin 43 channel inhibitory peptide

S. Yang, C. A. Clemett, M. A. Brimble, S. J. O'Carroll and P. W. R. Harris, RSC Med. Chem., 2020, 11, 1041 DOI: 10.1039/D0MD00172D

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements