Structure-function studies of motilin analogues.
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.
Miller
P
P
Centre de Recherche Clinique André Viallet, Hopital St. Luc, Université de Montréal, Canada.
Gagnon
D
D
Dickner
M
M
Aubin
P
P
St-Pierre
S
S
Poitras
P
P
D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D008969:Molecular Sequence Data; D009037:Motilin / Q000031:analogs & derivatives* / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D011817:Rabbits; D011869:Radioligand Assay; D013329:Structure-Activity Relationship
D009037:Motilin