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.