Solution structure of vasoactive intestinal polypeptide (11-28) -NH2, a fragment with analgesic properties
Haghjoo, K.; Cash, P.W.; Farid, R.S.; Komisaruk, B.R.; Jordan, F.; Pochapsky, S.S.
Peptide Research 9(6): 327-331
1996
ISSN/ISBN: 1040-5704 PMID: 9048428 Document Number: 457879
An 18-residue-long fragment of vasoactive intestinal polypeptide (VIP(11-28)-NH-2) that is known to be analgesic was synthesized by solid-phase t-Boc methodology on a 4-methylbenzhydrylamine resin. Circular dichroism spectroscopy gave evidence that the peptide acquires about 60% helical structure in 50/50 methanol/phosphate buffer, pH 6.0, and 65% (+-5%) helicity in 80/20 methanol/phosphate buffer pH 7.0. A 2.0 mM solution of VIP(1128)-NH-2 in 80% methanol, 20% phosphate buffer pH 7.0 was subjected to 2-dimensional nuclear magnetic resonance (NMR) studies. The NMR results suggested formation of an extended helical structure extending from residue 11 to 27, essentially the same region found to be helical in a VIP(1-28)-NH-2 analog. This finding suggests that the sequence required for analgesia assumes a helical structure at the receptor.