LYSINE VASOPRESSIN UNDERGOES RAPID GLYCATION IN THE PRESENCE OF REDUCING SUGARS

Lysine vasopressin (LVP) readily reacts with reducing saccharides both in lyophilized preparations and in aqueous solution, incubation of LV P with, for example, lactose over a pH range of 3.0-8.5 in phosphate b uffer or simply in water, gives rise to a number of reaction products, some of which form rapidly (in a matter of hours) even in the frozen state. Reaction mixtures were analysed by reversed-phase HPLC and the structures of the products were deduced from the amino-acid compositio n of isolated components, by comparison with product profiles obtained with analogues under similar conditions and by FAB mass-spectral anal ysis of derivatives isolated after reduction with cyanoborohydride. Th e primary products arise from the formation of Schiff's bases at one o r both of the two amino functions. The alpha-amino group of the N-term inal cystine is considerably more reactive than is the epsilon-amino g roup of lysine and it is the N-terminal adduct which rapidly forms eve n at -20 degrees C. It is concluded that caution must be shown in usin g reducing sugars in formulations containing peptides and proteins, pa rticularly the vasopressins and oxytocin.