THE NEW ERA OF BIOTECH INSULIN ANALOGS

Many of the structural properties of insulin have evolved in response to the requirements of biosynthesis, processing, transport and storage in the pancreatic beta cells, properties that are not necessary for t he biological action of the hormone. It is therefore not surprising th at wild-type insulin has far from optimal characteristics for replacem ent therapy. For example, native human insulin self-associates to hexa meric units, which limits the possibilities for the absorption of the molecule by various routes. During the last decade new techniques of m olecular design have emerged and recombinant DNA technology offers new and exciting opportunities for rational protein drug design. This rev iew describes examples of recent advances in insulin engineering aimed at optimizing the hormone for therapy. Such approaches focus on impro vements in the pharmacokinetic properties, storage stability, and feas ibility for less intrusive routes of administration.