Synthesis of the porcine intestinal peptide PHI and its 24-glutamine analogue

Abstract

PHI--a new candidate hormone from porcine intestinal tract-- corresponds to a linear heptacosapeptide amide of remarkable sequence homology to the known members of the glucagon family, particularly to the vasoactive intestinal peptide (VIP) and secretin. The position 24 usually occupied by an aminodicarboxylic acid omega-amide, in the present case, however, carries a glutamic acid, thus opening the question of whether this structural feature is related to desamidation in one of the isolation and characterization steps or of whether it is significant for this peptide factor. Consequently the heptacosapeptide amides corresponding to the proposed primary structure and to its 24-glutamine analogue have been synthesized. Comparative chromatographic and biological studies on the natural and the two synthetic products have confirmed the correctness of the primary structure proposed for the isolated PHI. Since [24-glutamic acid] and [24-glutamine]PHI exhibit no significant differences in their biological potencies, the main question is still open of whether the position 24 in native PHI is occupied by the aminodicarboxylic acid omega-amide (glutamine) or by N-substituted derivatives (N-glycosyl).