Synthesis and biological evaluation of S-lipidated lipopeptides of a connexin 43 channel inhibitory peptide. Issue 9 (10th July 2020)

• Record Type: Journal Article
• Authors: Yang, Sung-Hyun; Clemett, Connor A.; Brimble, Margaret A.; O'Carroll, Simon J.; Harris, Paul W. R.
• Is Part Of: RSC medicinal chemistry. Volume 11:Issue 9(2020)
• Page Start: 1041
• Page End: 1047
• Publication Date: 2020-07-10
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1039/d0md00172d
• Languages: English
• ISSNs: 2632-8682

Abstract

Abstract : Lipidated Peptide5 analogues are able to mediate hemichannel openings leading to inhibition of chemical messengers to the extracellular matrix. 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.