biostudies-literatureYang SHAuckland Medical Research Foundation1041-1047https://www.ebi.ac.uk/biostudies/studies/S-EPMC7513673biostudies-literatureUnknown11(9)The synthesis and biological activity of 42 novel <i>S</i>-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 <i>S</i>-lipidation to afford <i>S</i>-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.RSC medicinal chemistrySynthesis and biological evaluation of <i>S</i>-lipidated lipopeptides of a connexin 43 channel inhibitory peptide.PMC75136731117016O'Carroll SJYang SHBrimble MAClemett CAHarris PWRfalseSynthesis and biological evaluation of <i>S</i>-lipidated lipopeptides of a connexin 43 channel inhibitory peptide.The synthesis and biological activity of 42 novel <i>S</i>-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 <i>S</i>-lipidation to afford <i>S</i>-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.2020-01-01T00:00:00Z2020 Sep2026-05-07T19:15:43.407Z2025-05-18T13:36:13.715ZS-EPMC75136733347969610.1039/d0md00172d