STRUCTURE OF ACETONE-LYSINE-VASOPRESSIN AS ESTABLISHED THROUGH ITS SYNTHESIS FROM ACETONE DERIVATIVE OF S-BENZYL-L-CYSTEINYL-L-TYROSINE

Acetone-lysine-vasopressin, an isopropylidene derivative resulting from the inactivation of the hormone by acetone, has been synthesized from the acetone derivative of S-benzyl-L-cysteinyl-L-tyrosine. This isopropylidene dipeptide was first coupled with L-phenylalanyl-L-glutaminyl-L-asparaginyl-S-benzyl-L-cysteinyl-L-prolyl-N∑-tosyl-L-lysylglycinamide by the mixed anhydride procedure. The resulting nonapeptide derivative was then converted to acetone-lysine-vasopressin by removal of the tosyl and the benzyl groups with sodium in liquid ammonia and subsequent oxidation of the resulting disulfhydryl compound with potassium ferricyanide. Isolation and purification of the synthetic acetone-lysine-vasopressin was accomplished by partition chromatography on Sephadex. Extensive comparison of the physical and chemical properties, as well as the pressor activity (6-7 units/mg), of the synthetic material with those of acetone-lysine-vasopressin prepared from lysine-vasopressin and acetone showed the two compounds to be identical. Since the acetone derivative of S-benzyl-L-cysteinyl-L-tyrosine has been shown previously to be a substituted 2,2-dimethyl-4-imidazolidinone, it may be concluded that acetone-lysine-vasopressin possesses the same imidazolidinone ring structure in which the isopropylidene group from acetone forms a bridge between the nitrogen atom of the free amino group of the half-cystine residue at position 1 in lysine-vasopressin and the nitrogen of the peptide bond between this half-cystine residue and the tyrosine residue at position 2. © 1969, American Chemical Society. All rights reserved.