Increased affinity of insulin for its receptor following conjugation to a second protein

It has been observed that various glutaraldehyde linked conjugates of insulin and bovine serum albumin display enhanced binding to the insulin receptor. High molecular weight covalent complexes resulting from the conjugation of insulin to both N-acylurea albumin and unmodified albumin have been shown to displace (125I-TyrA14) human insulin from HepG2 cell receptors successfully. Results indicate that their affinity for the insulin receptor is greater than that of insulin itself by an order of magnitude. The relationship between these results and similar insulin binding phenomena reported by other workers ('super-activity') is examined, particularly with regard to possible alterations to the insulin binding site brought about by the respective conjugation procedures. It is suggested that modifications to the B29 lysine residue might play a crucial role in stabilising the interaction of conjugated insulin with its cognate receptor. The powerful potential of insulin to act as carrier in the intracellular delivery of drugs and other molecules is discussed.