Synthesis and Analgesic Activity of Cholecystokinin-Heptapeptide Analogs with N-Terminal Substitution

抄録

Analogs of Cholecystokinin-heptapeptide (CCK-7), i.e., two epimers of 3-(-sulfooxyphenyl)-2-methylpropanoyl-Met-Gly-Trp-Met-Asp-Phe-NH₂, two epimers of 3-(4-sulfooxyphenyl)-2-methylpropanoyl-Nle-Gly-Trp-Met-Asp-Phe-NH₂ and [D-Try(SO₃H)¹]-CCK-7, were prepared by the solution method. The analgesic effects of these analogs were measured by means of the writhing test. These analogs produced analgesic effects after subcutaneous injection in mice. The replacement of the tyrosine(O-sulfate) residue at position 1 by a 3(4-sulfooxyphenyl)-2-methyl-propanoyl group enhanced the analgesic effect, and the configuration of these residues hardly influenced the effect. On the other hand, the replacement of the L-methionine residue at position 2 by an L-norleucine residue in addition to the exchange of the tyrosine(O-sulfate) residue at position 1 for a 3-(4-sulfooxyphenyl)-2-methylpropanoyl group reduced the activity.