Structure-function studies of motilin analogues.

P Miller; D Gagnon; M Dickner; P Aubin; S St-Pierre; P Poitras

doi:10.1016/0196-9781(94)00148-y

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Structure-function studies of motilin analogues.

P Miller·D Gagnon·M Dickner·P Aubin·S St-Pierre·P Poitras

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Abstract

Over 100 motilin fragments and analogues, including monosubstituted C-terminal-deleted analogues, conformationally restricted analogues, analogues with peptide bond isoteres (CH2-NH), and N-terminal fragments adjunct to an amphiphilic helix, were synthesized by solid-phase methodology, purified by reverse-phase HPLC, and assayed in vitro in a muscle strip bioassay (rabbit duodenum) and in a radioligand binding assay on crude membrane extracts from smooth muscle (rabbit antrum). The data suggest the existence of three distinct regions involved in the interaction of motilin with its receptor: the N-terminal region (amino acids 1-7) constitutes the minimal basic unit of binding and activity; the transition region (amino acidsa 8-9) links the N-terminal and C-terminal regions; and the C-terminal region (amino acids 10-22) forms an alpha-helix that stabilizes the interaction of the N-terminal residues at the active site.

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Amino Acid Sequence Animals Female Molecular Sequence Data Motilin Muscle Contraction Rabbits Radioligand Assay Structure-Activity Relationship Comparative Study Journal Article Research Support, Non-U.S. Gov't

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P Miller, D Gagnon, M Dickner, P Aubin, S St-Pierre, P Poitras. 1995. Structure-function studies of motilin analogues.. https://doi.org/10.1016/0196-9781(94)00148-y

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