The thrust of this proposal is directed at establishing the molecular basis of protein-carbohydrate interactions using the paradigm of the carbohydrate-binding proteins of plant and animal origin (lectins). The underlying hypothesis is that such binding involves specific, well-defined interactions between functional groups of the carbohydrate ligand in its ground-state structure and matching groups in the protein forming a specific binding site, which provides for any degree of specificity of a lectin for a specific carbohydrate ligand. The application of lectin- carbohydrate binding to biomedical problems is a significant consideration of our studies. Several new techniques that provide unique new approaches for studying protein-carbohydrate interaction include submicro frontal chromatography analysis, surface plasmon resonance, and mathematical modeling of the combining sites of lectins. Another innovation is an extension of our successful study of DNA-carbohydrate interaction in which we will attempt to obtain nucleic acid aptamers to human blood group substances and the bacterial polysaccharide from E.coli 0139 which causes """"""""traveler's disease."""""""" Among the objectives we plan to pursue are a search for (and isolation and characterization) of new lectins, with unique and useful properties; a physical-chemical characterization of the sialic acid binding slug lectin, including expression of the recombinant proteins in a eukaryotic expression system, NMR measurements of the binding of methyl N-acetylneuraminic acid alpha-ketoside and a solution of its X-ray crystal structure complexed with neuraminic acid; the X-ray crystal structure of the Man alpha1-3 Man-specific crocus lectin complexed with its disaccharide, and its use as a histochemical stain for animal cells and tissues; and attempts to label the carbohydrate binding sites of several lectins using photoaffinity labels.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Physiological Chemistry Study Section (PC)
Program Officer
Marino, Pamela
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Michigan Ann Arbor
Schools of Medicine
Ann Arbor
United States
Zip Code
Wearne, Kimberly; Winter, Harry C; Goldstein, Irwin J (2013) Isolation of banana lectin-a practical scale procedure from ripe banana fruit. Prep Biochem Biotechnol 43:285-92
Yue, Tingting; Goldstein, Irwin J; Hollingsworth, Michael A et al. (2009) The prevalence and nature of glycan alterations on specific proteins in pancreatic cancer patients revealed using antibody-lectin sandwich arrays. Mol Cell Proteomics 8:1697-707
Grahn, Elin M; Winter, Harry C; Tateno, Hiroaki et al. (2009) Structural characterization of a lectin from the mushroom Marasmius oreades in complex with the blood group B trisaccharide and calcium. J Mol Biol 390:457-66
Lim, Sing Fee; Lee, May May; Zhang, Peiqing et al. (2008) The Golgi CMP-sialic acid transporter: A new CHO mutant provides functional insights. Glycobiology 18:851-60
Wearne, Kimberly A; Winter, Harry C; Goldstein, Irwin J (2008) Temporal changes in the carbohydrates expressed on BG01 human embryonic stem cells during differentiation as embryoid bodies. Glycoconj J 25:121-36
Goldstein, Irwin J; Winter, Harry C; Aurandt, Jennifer et al. (2007) A new alpha-galactosyl-binding protein from the mushroom Lyophyllum decastes. Arch Biochem Biophys 467:268-74
Arigi, Emma; Singh, Suddham; Kahlili, Ardalan H et al. (2007) Characterization of neutral and acidic glycosphingolipids from the lectin-producing mushroom, Polyporus squamosus. Glycobiology 17:754-66
Grahn, Elin; Askarieh, Glareh; Holmner, Asa et al. (2007) Crystal structure of the Marasmius oreades mushroom lectin in complex with a xenotransplantation epitope. J Mol Biol 369:710-21
Wearne, Kimberly A; Winter, Harry C; O'Shea, Katherine et al. (2006) Use of lectins for probing differentiated human embryonic stem cells for carbohydrates. Glycobiology 16:981-90
Grahn, Elin; Holmner, Asa; Cronet, Cecilia et al. (2004) Crystallization and preliminary X-ray crystallographic studies of a lectin from the mushroom Marasmius oreades. Acta Crystallogr D Biol Crystallogr 60:2038-9

Showing the most recent 10 out of 86 publications