Vasoactive intestinal polypeptide precursors have highly potent bronchodilatory activity.
We studied the structure-activity relationships of vasoactive intestinal polypeptide (VIP) to determine whether there were active forms of C-terminal-free VIP, so that suitable structures could be identified and produced by recombinant technology. We found that some presumptive VIP precursors prepared by solid-phase synthesis exhibited a higher biological activity than natural VIP both in vitro and in vivo, although we could not determine the actual active fragment. VIP-Gly-Lys-OH and VIP-Gly-Lys-Arg-OH, which were extended from the C-terminal of mature VIP, demonstrated a respective 210% and 160% increase in bronchodilatory activity in comparison to the activity of natural VIP. Furthermore, these peptides exhibited a respective 110% and 130% increase in hypotensive activity when compared with VIP itself.
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Eisai Tsukuba Research Laboratories, Eisai Company Ltd., Ibaraki, Japan.
Tachibana
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D000595:Amino Acid Sequence; D000818:Animals; D001993:Bronchodilator Agents; D006168:Guinea Pigs; D007022:Hypotension / Q000139:chemically induced; D066298:In Vitro Techniques; D008297:Male; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D011498:Protein Precursors / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D001993:Bronchodilator Agents; D010455:Peptides; D011498:Protein Precursors; D014660:Vasoactive Intestinal Peptide