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TitleScreening, synthesis and structural characterization of a novel bicyclic peptide inhibiting α7 nicotinic acetylcholine receptor.
Journal, issue, pagesChem Commun (Camb), Year 2026
Publish dateAug 10, 2026
AuthorsXichu Yang / Kele Cui / Xiuxiu Cao / Haopeng Chen / Changlin Tian / Demeng Sun /
PubMed AbstractPeptides targeting the α7 nicotinic acetylcholine receptor (α7-nAChR) represent promising candidates for therapeutic and chemical probe development. Here, we identified a novel bicyclic peptide ...Peptides targeting the α7 nicotinic acetylcholine receptor (α7-nAChR) represent promising candidates for therapeutic and chemical probe development. Here, we identified a novel bicyclic peptide KP1877 phage-displayed peptide library screening followed by chemical synthesis of active analogs. Structural characterization reveals KP1877 adopts a unique bicyclic conformation distinct from known natural α7-nAChR-targeting peptides, and exerts potent inhibitory effect by stabilizing the closed, non-conducting state of the receptor orthosteric binding.
External linksChem Commun (Camb) / PubMed:42574057
MethodsEM (single particle)
Resolution2.71 Å
Structure data

82114

43sn

EMDB-82114, PDB-43sn:
Alpha-7 nicotinic acetylcholine receptor bound to inhibitory bicyclic peptide KP1877 in a resting state
Method: EM (single particle) / Resolution: 2.71 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-HOH:
WATER

Source
  • homo sapiens (human)
  • synthetic construct (others)
KeywordsMEMBRANE PROTEIN / nicotinic acetylcholine receptor

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