Synthesis and Biological Activity of Analogs of Substance P, Modified for Conformational Information by D-Amino Acids.

Abstract

Eight analogs of substance P (SP) were synthesized by an automated solid phase-technique. Three analogs are undecapeptides, as is SP, and 5 are heptapeptides. Phe7 of SP is significant for activity, but Phe8 is not. Gly9 of SP, when replaced by D-Leu, resulted in a desirable loss of activity toward the design of antagonists. Three of the 5 heptapeptides have single D-amino acid substitution and the other two have 2 D-amino acid substitutions. Those 3 heptapeptides, having a D-amino acid in the position corresponding to Gly9 of SP, had the desirable lowest agonist activity. [D-Phe7]-SP had antagonist activity which was weak, probably because it also had low agonist activity.