Abstract
A series of novel tetra-peptide motilin agonists, having the general structure H-Phe-Val-X-Ile-NH(2), were designed, on the basis of structure-activity relationship studies of motilin. Peptides, in which X is a side chain substituted tryptophan residue, have agonistic activity. H-Phe-Val-Trp(2'-CH(2)CH(2)OH)-Ile-NH(2)(7), H-Phe-Val-Trp(2'-SCH(3))-Ile-NH(2)(8), and H-Phe-Val-Trp(2'-SCH(2)CH(2)CH(3))-Ile-NH(2)(9), showed an EC(50) for contractile activity in the rabbit smooth muscle of 14.1+/-3.2, 12.9+/-4.1, and 4.6+/-1.6 microM, respectively. Interaction of the tryptophan aliphatic side chain with motilin receptor appears to influence the signal transduction via motilin receptor.
MeSH terms
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Amino Acid Sequence
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Animals
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Drug Design*
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Gastrointestinal Agents / chemical synthesis
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Gastrointestinal Agents / chemistry
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Gastrointestinal Agents / metabolism
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Gastrointestinal Agents / pharmacology
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Gastrointestinal Motility / drug effects
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Intestines / drug effects
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Intestines / physiology
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Male
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Motilin / agonists*
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Motilin / metabolism
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Motilin / pharmacology
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Muscle Contraction / drug effects
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Muscle, Smooth / drug effects
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Muscle, Smooth / physiology
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Oligopeptides / chemical synthesis*
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Oligopeptides / chemistry
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Oligopeptides / metabolism
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Oligopeptides / pharmacology*
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Rabbits
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Receptors, Gastrointestinal Hormone / metabolism
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Receptors, Neuropeptide / metabolism
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Signal Transduction
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Structure-Activity Relationship
Substances
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Gastrointestinal Agents
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Oligopeptides
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Receptors, Gastrointestinal Hormone
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Receptors, Neuropeptide
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motilin receptor
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Motilin