Allomalformin.

In an attempt to find explanation for the initial erroneous sequence assignment for malformin, a sequence-isomer of the natural product, 3-isoleucine-5-valine malformin or briefly "allomalformin" that on partial acid hydrolysis could have given rise to misleading fragments, was synthesized and compared with both natural and synthetic preparations of malformin. Allomalformin is identical to the parent microbial peptide (malformin A, or briefly malformin) with respect to biological activity and conformation (ORD and CD spectra) and is indistinguishable from it by high pressure liquid chromatography. Yet, the two isomers have slightly different Rf values on thin-layer chromatograms and by this method no allomalformin could be detected in samples of the natural product. On the other hand both high pressure liquid chromatography and thin-layer chromatography demonstrated the presence of the lower homolog, 5-valine malformin, in the samples examined. On partial acid hydrolysis this natural analog should liberate Val-Cys, while Cys-Val forms from malformin itself. Similarly, the corresponding desthio cyclopentapeptides should give rise to Val-Ala and Ala-Val respectively; the former being more resistant to further hydrolysis persists in the partial hydrolysates. The presence of Val-Cys in partial hydrolysates of malformin and of Val-Ala in the partial hydrolysates of desthiomalformin, both originating from the accompanying lower homolog rather than from malformin itself, is likely to have led to the postulation of the erroneous Cys-Val-Cys partial sequence.

Synthesis and pharmacological properties of the N-terminal decapeptide of the vasoactive intestinal peptide (VIP).

The decapeptide derivative, L-histidyl-L-seryl-L-aspartyl-L-alanyl-L-valyl-L-phenylalanyl-L-threonyl-L-aspartyl-L-asparaginyl-L-tyrosine methyl ester, corresponding to the N-terminal sequence of both porcine and chicken VIP was synthesized in solution, by the stepwise strategy. Its pharmacological properties resemble those of VIP itself, but with a much lower potency, comparable to that of peptides with C-terminal sequences. The presence of two independent sequences carrying similar instructions was recognized in VIP.