SYNTHESIS AND BIOLOGICAL ACTIVITY OF SUBSTANCE P ANALOGS

Substance P (SP) and its three analogs were synthesized through solid-phase procedure. The fully-protected peptideresin was cleaved with anhydrous HF. -SH of Cys in Cys^5,9 SP(4-11) was protected with Acm, then deprotected through Iodine oxdation method, the disulfide bridge cyclization was formed subsequently. The crude product was purified on C₁₈ RP-HPLC. The results of guinea-pig isolated ileum test (GPI) showed that the potency of the analogs was as follows: AcGln⁵,Pro⁹ SP(5-11) > SP > SP(4-11) > Cys^5,9 SP(4-11). They induced GPI to contract very fast and showed the characteristics of tachykinin. On the writhing test in mice, the results showed: Cys^5,9 SP(4-11) > SP > SP(4-11) > AcGln⁵,Pro⁹ SP(5-11). The biological tests showed that the SP analogs have some extent of selectivity.