Synthesis and biological properties of insulin-deoxycholic acid chemical conjugates.

Bile acids have been considered very useful in the preparation of new pharmaceuticals, and more recently in the preparation of peptide and protein drugs because of their natural chemical and biological properties. In this study, we modified recombinant human insulin by covalently attaching deoxycholic acid (DOCA) derivatives in order to synthesize orally active insulin analogues. DOCA derivatives, namely succinimido deoxycholate and succinimido bisdeoxycholyl-l-lysine were prepared and site specifically conjugated at LysB29 of insulin. The resultant insulin conjugates, [NB29−deoxycholyl] insulin (Ins−DOCA) and [NB29−bisdeoxycholyl-l-lysil] insulin (Ins−bisDOCA), were studied for their chemical, structural, and biological properties. Their chemical properties were determined by HPLC, MALDI-TOF mass spectroscopy, and dynamic light scattering. Lipophilicity and self-aggregation behavior of insulin conjugates were enhanced with increasing number of labeled bile acid. The far-ultraviolet region of circular dic...