Chemical Protein Synthesis: Inventing New Chemistries to Reveal How Proteins Work

摘要

Proteins are the 'natural products' of our era, and now play the same role as targets for synthetic organic chemistry that plant and microbial natural products played in the second half of the 20~(th) century. Millions of proteins are being discovered at the DNA level as predicted open reading frames,. bv highly automated genome and metaeenome sequencing I'll. Numerous proteins are also being identified by mass spectrometry from a variety of natural sources such as the venoms of spiders, snakes, and cone snails [2]. It has been estimated that there are between 10~5 and 10~6 unique venom-derived proteins alone [3]. Many of- these venom-derived proteins have post-translational modifications that are essential for biological activity. The challenge for chemists in the current era is to develop synthetic methods that are powerful enough to enable the straight-forward preparation of predicted proteins and post-translationally modified protein molecules, of defined structure and high purity, in order to elucidate and control the molecular basis of the diverse biological activities of protein molecules. Here I will briefly present a set of scientific ideas and consequent synthetic methods that have enabled the general application or chemistry to proteins. Selected case studies will be used to illustrate the application of synthetic chemistry to elucidate the molecular basis of protein function