SBIR-STTR Award

The aim of this Phase I proposal is to synthesize amphipathic polymer amphipols. These materials will be evaluated as a detergent to solubilize membrane proteins in aqueous solutions without deleteriously increasing the effective molecular weight of the protein. In the first amphipuls described in the latter will be resynthesized and evaluated. If effective, molecular modifications will be made in the amphipols in an attempt to tailor them for specific solubilization tasks. Note this proposal is submitted in collaboration with Dr. Charles R. Sanders whose laboratory is supplying equipment and staff to evaluate the amphipoly protein structure by solution NMR materials. PROPOSED COMMERCIAL APPLICATIONS: The possibility of using the materials proposed here to study protein structure in solution via NMR is especially appealing since no such materials are available commercially. Anatrace has a history of timely introduction of new, useful detergents and other biochemicals to the international technical community.

Ainphipols are low molecular weight (<20 kDa) linear polymers having a distribution of polar and hydrophobic side chains which confers amphipaticity to the polymer. Amphipols represent a unique way of solubilizing integral membrane proteins. Amphipols wrap themselves around the hydrophobic transmembrane domains of membrane proteins so that the hydrophobic side chains of the polymer stabilize the hydrophobic surface of the protein, while the polar side chains of the polymer confer aqueous solubility to the protein-amphipol complex In Phase I a new and simpler route to the only existing family of amphipols was developed and an entirely new and potentially useful family of amphipols was discovered. In Phase II we plan to synthesize and characterize a number of variations of this family (called PMALT). These new molecules will be evaluated in the laboratory of Dr. Charles R. Sanders for their ability to solublize, stabilize, and maintain the functionality of membrane proteins. The study will provide the basis for future unique applications of amphipols in structural biology biochemistries, biomedicine, and biotechnology. PROPOSED COMMERCIAL APPLICATION: The possibility of using the materials proposed here to study membrane protein structure in solution via NMR is especially appearing. Amphipols may also provide the basis for new approaches in drug delivery, biosensors, and other biomedical/ technological applications. Presently, there is no commercial source for amphipol- class polymers. Anatrace has a history of timely introduction of new, useful detergent and other biochemicals to the international technical community.