Office: JSCBB C125
Lab: JSCBB C165, C175
Lab Phone: 303-735-7993
Ph.D.: Columbia University 2005
Postdoctoral Fellow: Memorial Sloan-Kettering Cancer Center 2005-2011
Bio-Organic, Bio-Inorganic, Chemical Biology/Genetics, Proteins & Enzymology, Chemical Biology/Genetics, Synthesis, Biochemistry
Our lab uses chemical approaches to study the effects of glycosylation on protein structure, function, and stability. Within complex biological systems, glycans serve as key structural and functional elements. More and more evidence has pointed to the importance of protein glycosylation in human health and disease. It is imperative, therefore, to investigate and document the function of glycans on therapeutically important proteins. However, because protein glycosylation is not under direct genetic control, heterogeneity in the structure of glycans is an inherent property of glycoproteins. This inherent structural diversity potentially parallels a vast number of functions and makes it very difficult to analyze the role of glycosylation. Therefore, obtaining homogeneous glycoproteins is necessary for functional analysis of protein glycosylation. Recently, several approaches, including glycosylation pathway engineering, glycan remodeling, and chemical synthesis have established the feasibility of preparing homogeneous glycoproteins in response to pre-selected oligosaccharides. Although biological methods are more practical means by which to obtain large homogeneous glycoproteins, and to produce glycoproteins on preparative scales, they are severely limited with respect to the incorporation of O- and N-glycans with different structures at different glycosylation sites. Chemical synthesis offers greater flexibility for studying the function of the differently glycosylated molecular forms (glycoforms) of small soluble glycoproteins. Synthesis represents a more convenient means by which to accomplish glycan structural modifications and small-scale preparations. Since chemical glycosylation is not dictated by the amino acid sequences of proteins, it also allows the generation of glycoproteins with “unnatural” amino acids or “unnatural” glycans, or glycoproteins with “unnatural” glycosylation sites.
4. L. Chen, M.R. Drake, M.G. Resch, E.R. Greene, M.E. Himmel, P.K. Chaffey, G.T. Beckham,* Z. Tan,* (2014) Specificity of O-glycosylation in enhancing the stability and cellulose binding affinity of Family 1 carbohydrate-binding modules. Proc Natl Acad Sci USA, 111:accepted.
3. C.M. Payne, M.G. Resch, L. Chen, M.F. Crowley, M.E. Himmel, L.E. Taylor, M. Sandgren, J. Ståhlberg, I. Stals,* Z. Tan,* G.T. Beckham,* (2013) Glycosylated linkers in multi-modular lignocellulose degrading enzymes dynamically bind to cellulose. Proc Natl Acad Sci USA, 110:14646-14651.
2. X. Guan, M.R. Drake, Z. Tan* (2013) Total synthesis of human galanin-like peptide through an aspartic acid ligation. Org Lett 15:6128–6131.
1. L. Chen, Z. Tan* (2013) A convenient and efficient synthetic approach to mono-, di-, and tri-O-mannosylated Fmoc amino acids. Tetrahedron Lett 54:2190-2193.