New chemical reactions for site-selective protein modification

ORGN 61

Matthew B. Francis, francis@cchem.berkeley.edu, Department of Chemistry, University of California, Berkeley, 724 Latimer Hall, Berkeley, CA 94720-1460
The broad utility of protein bioconjugates has created a need for new and diverse strategies for site-selective protein modification. In particular, chemical reactions that target alternative amino acid side chains or unnatural functional groups are emerging as a valuable complement to more commonly used lysine and cysteine based strategies. Recently we have reported several new reactions that can modify proteins under mild aqueous buffer conditions, including a three-component Mannich-type coupling reaction for tyrosine residues, tryptophan modification using rhodium carbenoids, the attachment of lipids to tyrosine residues using pi-allylpalladium complexes, and a simple biomimetic strategy for the functionalization of the N-termini. The scope and applications of these new strategies will be discussed, as well as the reaction design concepts that are emerging from these studies.