Synthesis and some Pharmacological Properties of an Immunoactive Lysine-Containing Tetrapeptide

摘要

The potentially immunoactive lysine-containing tetrapeptide H-Lys-Ala-Val-Gly-OH was synthesized. The value of using a method based on mixed anhydrides and activated esters to obtain tetrapeptide at high yield was demonstrated. The peptide preparation method was improved by replacing p-nitrophenyl esters at the intermediate stage with N-hydroxysuccinimide esters, yielding a crystalline substance at high purity, and replacing the BOC (tert-butyloxycarbonyl) group for protection with a carbobenzoxy group, which provided for a one-step removal of the protection of both amino groups in mild conditions. Comparative assessment of the immunological activity of the tetrapeptide on the background of immunization with sheep erythrocytes in mice with other lysine-containing tetrapeptides showed it to have more marked immunostimulatory activity. Studies of acute and chronic toxicity demonstrated the absence of toxic activity in the lysine-containing tetrapeptide studied here on s.c. administration to experimental animals. The tetrapeptide corresponded to toxicity class 5, i.e., it was essentially nontoxic.