Research Focus
Development & Utilization of Methods to Incorporate Unnatural Chemical Groups into Proteins.

We have developed a chemical approach for the production of the large polypeptide chains that comprise protein molecules, enabling us to change the structure of a protein in ways impossible by natural means. We use solid phase peptide synthesis to generate peptides up to ~50 amino acids in length and then assemble them using chemoselective reactions to make proteins up to ~150 amino acids in length. This-chemical ligation-approach greatly facilitates the synthesis of proteins of moderate size and has opened the world of proteins to the synthetic tools of organic chemistry. Chemical ligation can be extended to biologically expressed proteins enabling the semisynthesis of proteins of unlimited size that contain fluorophores or cross-linking agents at defined positions. Our goal is to introduce non-coded amino acids and other chemical groups into proteins to better understand the molecular basis of protein function.