Novel Detergents for Crystallizing Membrane Proteins

Period of Performance: 03/17/1993 - 08/31/1994

Unknown

Phase 2 SBIR

Recipient Firm

Anatrace, Inc.
Cleveland, OH 44128
Principal Investigator

Abstract

DESCRIPTION: (Adapted from the investigator's abstract.) The understanding of protein function is greatly enhanced by the availability of three-dimensional structural information obtained by X-ray crystallography. Unfortunately, the large, well-ordered three-dimensional crystals required for X-ray analyses have been difficult to produce for membrane proteins since they tend more naturally to form two-dimensional arrays. A further complicating factor in dealing with membrane proteins is the requirement for detergents to solubilize and stabilize the native structure. Although crystallization of membrane proteins is more of an art than a science as yet, it is clear that the structure and purity of the detergent are critical factors. In Phase I the applicants synthesized, purified and evaluated a homologous series of novel substituted glucosides and maltosides that have a hydorophobic tail of varying degrees of rigidity. Many of these detergents extracted cytrochromes in active form. In Phase II they will synthesize more detergents with rigid tails making a total of 20 to 24. The utility of these detergents will be evaluated by their ability to extract in active form three different types of membrane proteins. The best candidates will be investigated for their ability to crystallize membrane proteins.