A new antiarrhythmic peptide, N-3-(4-hydroxyphenyl)propionyl Pro-Hyp-Gly-Ala-Gly

In order to increase the antiarrhythmic activity of Pro-Hyp-Gly-Ala-Gly (P-5), P-5 analogues with three different hydrophobic substituents, N-3- (4-hydroxyphenyl) propionyl (H), N-3-phenyl-propionyl (I) and N-3-phenylpropyl (P), were prepared and their activities were evaluated in CaCl2-induced arrhythmias in mice. HP-5 showed potent antiarrhythmic activity at 1 mg/kg, i.v. and its potency was much higher than that of P-5 at 10 mg/kg, i.v. IP-5 showed similar potency to P-5, but PP-5 was inactive. Pro-Hyp-Gly-Ala, Pro-Hyp-Gly and Pro-Hyp with the substituent, H, were also ineffective. Thus, 3- (4-hydroxyphenyl) propionylation of the imino nitrogen of Pro in P-5 led to increased potency.