WATER-SOLUBLE FATTY-ACID DERIVATIVES AS ACYLATING AGENTS FOR REVERSIBLE LIPIDIZATION OF POLYPEPTIDES

A novel method allowing the conjugation of a fatty acid to a peptide or protein in aqueous buffer is described in this paper, L-Cysteinyl 2-pyridyl disulfide (CPD) (III), which was obtained by reacting L-cysteine (I) with 2,2-dithiopyridine (II), was reacted with the N-hydroxysuccinimide ester of palmitic acid (IV) to yield a water-soluble derivative of palmitic acid, termed Pal-CPD (V), Pal-CPD (V) could be reacted with a sulfdryl-containing peptide or protein in aqeous buffer to yield the palmitic acid-derivatized conjugate (VI), The palmitic acid-derivatized Bowman-Birk protease inhibitor (BBI), synthesized using this conjugation method, was demonstrated to have 140-fold higher uptake into Caco-2 cell monolayers compared to native-BET, The biological activity of the conjugate, as assessed using an in vitro transformation assay, was retained.