Structure-activity relationships of sarafotoxins: chemical syntheses of chimera peptides of sarafotoxins S6b and S6c

The three chimera peptides of sarafotoxins S6b (SRTb) and S6c (SRTc), [Thr²SRTb, [Asn⁴]SRTb and [Glu⁹]SRTb, were synthesized chemically. From the comparisons of lethality, vasoconstrictor activity and receptor binding activity of SRTb, SRTa ([Asn¹³]SRTb), SRTc ([Thr²Asn⁴Glu⁹Asn¹³]SRTb), [Thr²SRTb, [Asn⁴]SRTb and [Glu⁹SRTb, it appears that the Lys⁹ to Glu⁹ substitution greatly diminishes these activities while the Lys⁴ to Asn⁴ substitution does not affect them, and the Ser² to Thr² substitution or the Tyr¹³ to Asn¹³ substitution slightly diminishes these activities. There results suggest that the very low activities of SRTc are caused mainly by the Lys⁹ to Glu⁹ substitution, but not by the Ser² to Thr² substitution, which was suggested to be responsible for the weak bioactivities of SRTd ([Thr²,Ile¹⁹]SRTb).