Insulin analogs for the treatment of diabetes mellitus: therapeutic applications of protein engineering.

ABSTRACT: The engineering of insulin analogs represents a triumph of structure-based protein design. A framework has been provided by structures of insulin hexamers. Containing a zinc-coordinated trimer of dimers, such structures represent a storage form of the active insulin monomer. Initial studies focused on destabilization of subunit interfaces. Because disassembly facilitates capillary absorption, such targeted destabilization enabled development of rapid-acting insulin analogs. Converse efforts were undertaken to stabilize the insulin hexamer and promote higher-order self-assembly within the subcutaneous depot toward the goal of enhanced basal glycemic control with reduced risk of hypoglycemia. Current products either operate through isoelectric precipitation (insulin glargine, the active comp

SUBMITTER: Berenson DF 

PROVIDER: S-EPMC3360579 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature