From peptide synthesis to chemical protein synthesis

ORGN 386

Stephen B.H. Kent, Department of Chemistry, Institute for Biohysical Dynamics, Department of Chemistry, Institute for Biohysical Dynamics, The University of Chicago, Cummings Life Sciences Center, 920 East 58th Street, Chicago, IL 60637
Total chemical synthesis of protein molecules is now a practical reality. The current state of the art will be presented, together with illustrative case studies. Features of an optimal CPS technology will be defined, and ways of achieving it will be suggested.

Topics to be discussed include: 1. What needs to be done to create an integrated set of practical technologies for the design, construction, and characterization of synthetic proteins, using chemistry. 2. What is being done already Ð the different approaches already found in the literature (including: solid phase chemical ligation; covalent capture; Fmoc SPS of peptide thioesters; etc.) 3. What remains to be developed Ðincluding convergent and Ôdomain ligationÕ chemistries for the construction of multi-domain proteins from pre-folded domain units as building blocks 4. Novel target proteins for chemical synthesis, in order to facilitate biophysical studies of the molecular basis of function.

Experimental support will be provided for the concepts put forward. This will constitute a road map to the creation of an optimized CPS technology.