4257-92-5Relevant academic research and scientific papers
Kinetics and Mechanism of the Facile Cyclization of Histidyl-prolineamide to Cyclo (His-Pro) in Aqueous Solution and the Competitive Influence of Human Plasma
Moess, Judi,Bundgaard, Hans
, p. 7 - 12 (2007/10/02)
A crucial point in the biosynthesis of cyclo (His-Pro), an endogenous and biologically active cyclic dipeptide, is the spontaneous cyclization of its precursor L-histidyl-L-prolineamide (His-ProNH2).In this study the kinetics and mechanism of the cyclization process has been investigated.His-ProNH2 was found to be converted quantitatively to cyclo(His-Pro) in aqueous solution at pH 2-10 and 37degC, the rate of cyclization being maximal at pH 6-7.Buffer substances such as phosphate (pH 6-7.4) were found to catalyse the cyclization.The bell-shaped pH-rate profile observed was accounted for by assuming spontaneous and specific acid- and base-catalysed reactions of the His-ProNH2 species in which the imidazole group is protonated and the primary amino group unprotonated.The much more rapid rate of cyclization of His-ProNH2 (t1/2 of 140 min at pH 6-7 and 37degC) relative to other proline-containing di- and tripeptides studied was suggested to be due to an intramolecular general acid catalytic effect by the protonated imidazole group.In the presence of human plasma enzymatic hydrolysis of His-ProNH2 competed with the cyclization and predominated greatly at 80percent plasma concentration.
