Synthesis and in vitro evaluation of [Leu13]porcine motilin fragments.
Several peptide fragments representing N-terminal, C-terminal, and internal sequences of [Leu13]porcine motilin ([Leu13]pMOT) were synthesized using Fmoc solid phase methodology. Peptides were assayed for motilin receptor binding activity in a rabbit antrum smooth muscle preparation and for stimulation of contractile activity in segments of rabbit duodenum. In vitro activity was directly correlated with motilin receptor binding affinity for all [Leu13]pMOT fragments examined. N-Terminal fragments of just over half the length of the native peptide are nearly equipotent as full-length motilin. These results suggest that the N-terminal segment, together with residues from the mid-portion of the molecule, constitutes the bioactive portion of pMOT. The C-terminal segment, in contrast, contributes little to receptor binding affinity or in vitro activity.
Macielag
M J
MJ
Boc Group Technical Center, Health Care Research, New Providence, NJ 07974.
Peeters
T L
TL
Konteatis
Z D
ZD
Florance
J R
JR
Depoortere
I
I
Lessor
R A
RA
Bare
L A
LA
Cheng
Y S
YS
Galdes
A
A
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000187:drug effects; D009037:Motilin / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000378:metabolism; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology*; D011706:Pyloric Antrum / Q000166:cytology / Q000187:drug effects; D011817:Rabbits; D011964:Receptors, Gastrointestinal Hormone / Q000378:metabolism*; D018013:Receptors, Neuropeptide; D013329:Structure-Activity Relationship; D013552:Swine
D000596:Amino Acids; D010446:Peptide Fragments; D011964:Receptors, Gastrointestinal Hormone; D018013:Receptors, Neuropeptide; C050802:motilin receptor; D009037:Motilin; C013087:13-Leu-motilin