We are exploring the discovery of new chemical reactions and synthetic strategies to develop a comprehensive, robust, and cost-effective methodology that would overcome the limits of biology to enable de novo chemical synthesis of any proteins found in nature or designed by humans. To this end, we are developing new chemistries of the following types: (1) easy-to-use peptide ligation chemistries for more efficient de novo synthesis of protein structural domains, (2) robust temporary structural support strategies for ligation and folding of challenging targets, and (3) efficient transpeptidative protein domain-domain ligation methods for multidomain proteins. 

Combined with the technologies of in vivo functional analysis, structural biochemistry, and drug development, our chemical protein synthesis methodology will support the study of human biology and health from a unique perspective, and facilitate the development of precision diagnostics and therapeutics. Indeed, the ability to synthesize structurally defined human proteoforms is essential for biomedical research on (1) dissection and reconstitution of human proteoform interaction networks, (2) mechanistic and functional elucidation of human proteoform interaction complexes, and (3) development and evaluation of drugs targeting human proteoforms.