ORGN 427 |
| The conjugation of small molecules to protein substrates is an important tool for the study and manipulation of protein function. In an effort to expand the current technology available for selective protein functionalization, we have developed two new bioconjugation reactions based on metallocarbene (1) intermediates. Treatment of vinyl-substituted diazo compounds with rhodium catalysts generates metallocarbenes in aqueous media at room temperature. Through proper selection of reaction co-solvents, solution additives, and rhodium catalysts, the metallocarbene intermediates can be selectively targeted to tryptophan residues, yielding 2, or to disulfide bonds generating adducts 3a-b. Despite competing reactions with water, efficient modification has been observed for both protein and peptide substrates, allowing for the site-selective incorporation of unnatural functional groups. This presentation will discuss the development and optimization of the reaction conditions, as well as characterization of the reaction products.
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Proteins, Peptides, Amino Acids, and Enzymes
1:00 PM-5:00 PM, Tuesday, 15 March 2005 Convention Center -- Room 25A, Oral
Division of Organic Chemistry |
