Synthesis and bioactivity of glycopeptides and peptide-protein conjugates
Thomas Tolbert
Associate Professor, The University of Kansas
Modification of the bioactivity of synthetic peptides using glycosylation and conjugation to proteins may expand their uses. N-linked glycosylation is a highly prevalent posttranslational protein modification that can alter the stability and biological activity of proteins. Attaching large N-linked glycans to synthetic peptides has the potential of altering their physicochemical properties and bioactivity as well. Synthesis of N-linked glycopeptides using on-resin coupling strategies, and studies of the effects of N-linked glycosylation on the bioactivity of glucagon and GLP-1 will be discussed. Conjugation of synthetic peptides to proteins can be used to combine advantages of solid phase peptide synthesis, such as the ability to incorporate non-natural amino acids or cyclic structures, with beneficial properties of proteins, such as extended in vivo lifetimes. The use of site-specific ligation methods to conjugate synthetic peptides to the N- and C-termini of antibody Fc fragments, and the application of these methods to develop bifunctional peptide inhibitor Fc fusion proteins for suppression of autoimmune responses will be presented.
Dr. Tolbert is an Associate Professor in the Department of Pharmaceutical Chemistry at The University of Kansas. He received his B.S. in Chemistry in 1991 from Purdue University and a Ph.D. in Biochemistry from MIT in 1998 under the supervision of James R. Williamson. From 1998 to 2003 he was a postdoctoral researcher at The Scripps Research Institute in La Jolla, CA under the supervision of Chi-Huey Wong. He joined the Department of Chemistry of Indiana University, Bloomington, IN as an Assistant Professor in 2003 and moved to The University of Kansas in 2011. The Tolbert lab research is focused on the synthesis of N-linked glycoproteins and glycopeptides, studying the role of glycosylation in immune responses and how glycosylation can alter the efficacy and stability of therapeutics.