H-Lys-Arg-Asn-Lys-Asn-Asn-OH is the minimal active structure of oxyntomodulin.
Oxyntomodulin inhibits gastric acid secretion via its C-terminal octapeptide. Its minimal active structure was delineated by testing, on histamine-stimulated gastric acid secretion in the conscious rat, the inhibitory effect of octapeptide analogues, shortened either or both on their N- or C- terminus. The octapeptide may be simplified by deleting the two C-terminal amino acids while keeping its efficacy and the slope of the dose-response curve. Suppressing the first N-terminal amino acid dramatically decreased the activity. The nonprotected peptides are metabolized by aminopeptidases and endopeptidases. The increased potency of the N-acetylated forms is related, at least in part, with their protection against aminopeptidases.
Carles-Bonnet
C
C
INSERM U 376, CHU Arnaud-de-Villeneuve, Montpellier, France.
Martinez
J
J
Jarrousse
C
C
Aumelas
A
A
Niel
H
H
Bataille
D
D
D000107:Acetylation; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D003243:Consciousness; D004305:Dose-Response Relationship, Drug; D005744:Gastric Acid / Q000378:metabolism*; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D004763:Glucagon-Like Peptides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D006207:Half-Life; D006632:Histamine / Q000494:pharmacology; D008297:Male; D053772:Oxyntomodulin; D010446:Peptide Fragments / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
D005765:Gastrointestinal Agents; D053772:Oxyntomodulin; D010446:Peptide Fragments; C101533:lysyl-arginyl-asparaginyl-lysyl-asparaginyl-asparagine; D004763:Glucagon-Like Peptides; D006632:Histamine