SOLUTION STRUCTURE OF VASOACTIVE INTESTINAL POLYPEPTIDE (11-28)-NH2, A FRAGMENT WITH ANALGESIC PROPERTIES

An 18-residue-long fragment of vasoactive intestinal polypeptide [VIP( 11-28)-NH2] that is known to be analgesic was synthesized by solid-pha se t-Boc methodology on a 4-methylbenzhydrylamine resin. Circular dich roism spectroscopy gave evidence that the peptide acquires about 60% h elical 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 s olution of VIP (11-28)-NH2 in 80% methanol, 20% phosphate buffer pH 7. 0 was subjected to 2-dimensional nuclear magnetic resonance (NMR) stud ies. The NMR results suggested formation of an extended helical struct ure extending from residue 11 to 27, essentially the same region found to be helical in a VIP (1-28)-NH2 analog. This finding suggests that the sequence required for analgesia assumes a helical structure at the receptor.