Lysine vasopressin undergoes rapid glycation in the presence of reducing sugars

J Pharm Biomed Anal. 1994 Nov;12(11):1355-61. doi: 10.1016/0731-7085(94)00098-0.

Abstract

Lysine vasopressin (LVP) readily reacts with reducing saccharides both in lyophilized preparations and in aqueous solution. Incubation of LVP with, for example, lactose over a pH range of 3.0-8.5 in phosphate buffer 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 composition of isolated components, by comparison with product profiles obtained with analogues under similar conditions and by FAB mass-spectral analysis of derivatives isolated after reduction with cyanoborohydride. The primary products arise from the formation of Schiff's bases at one or both of the two amino functions. The alpha-amino group of the N-terminal cystine is considerably more reactive than is the epsilon-amino group of lysine and it is the N-terminal adduct which rapidly forms even at -20 degrees C. It is concluded that caution must be shown in using reducing sugars in formulations containing peptides and proteins, particularly the vasopressins and oxytocin.

MeSH terms

  • Amino Acid Sequence
  • Chromatography, High Pressure Liquid
  • Freeze Drying
  • Glycosylation
  • Lactose / analysis
  • Lactose / chemistry*
  • Lypressin / chemistry*
  • Molecular Sequence Data
  • Temperature

Substances

  • Lypressin
  • Lactose