Chemists synthesize and screen massive library of nonnatural proteins. Such screens could yield protein drugs with advantages over natural ones
Chemists varied a nine-amino-acid string (green) in EETI-II. The protein's β-sheets are shown as flat, gray areas, and its disulfide bonds are indicated in yellow. Credit: Proc. Natl. Acad. Sci. USA Researchers have synthesized and screened a library of small proteins composed entirely of nonnatural amino acids. In these 29-amino-acid miniproteins, called xenoproteins because of their “foreign” content, all the natural l-amino acids were replaced with mirror-image d-amino acids. Such libraries could yield novel therapeutic agents with key advantages over natural protein-based drugs. Nonnatural miniproteins have enhanced temperature stability, making it easier to store and transport them without refrigeration, and the biomolecules resist enzymatic breakdown in the body. Bradley L. Pentelute and coworkers at Massachusetts Institute of Technology used combinatorial solid-phase synthesis to create a library of 200 million xenoproteins based ...