[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 [Cys5,9] SP(4-11) was protected with Acm, then deprotected through Iodine oxidation 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) > [Cys5,9] SP(4-11). They induced GPI to contract very fast and showed the characteristics of tachykinin. On the writing test in mice, the results showed: [Cys5,9] 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.
Liu
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SY
Institute of Parmaceutical Chemistry, PLA, Beijing 102205.
Zhong
M N
MN
Dong
Y X
YX
Li
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YL
Yuan
X M
XM
D000818:Animals; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects*; D013373:Substance P / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology
D013373:Substance P