Synthesis and protein conjugation studies of vitamin K analogues Original Research Article

Two vitamin K analogues bearing a carboxylic acid side chain (9a and its deuterated analogue 9b) were each synthesised in six steps from commercially available menadione. Analogue 9b was conjugated to lysozyme and bovine serum albumin (BSA) using EDCI/HOBT and by prior formation of its activated succinimidyl ester 11. Quantification of the thus formed conjugates by ESMS and LC–MS revealed that the number of equivalents of the analogue used in the couplings systematically controls the number of analogues that conjugate to the protein.