Peptide coupling experiments: Understanding the role of coupling reagents and amino acid sequence

ORGN 439

Travis Mickle, tmickle@nrpharma.com, Bindu Bera, Doug Linn, Christal Miller, Sven Guenther, Wendy Hirschelman, and Sanjib Bera. New River Pharmaceuticals, 1861 Pratt Drive, Suite 1090, Blacksburg, VA 24060
A set of N-terminal protected dipeptides were coupled with a C-terminal methyl ester of either alanine or isoleucine, using various common in situ coupling reagents. These included DCC, EDC, HBTU, TBTU, BOP, PyBrOP or TSTU. Standard coupling protocols for each coupling reagent were followed. After the usual work up, the crude tripeptides were analyzed by reverse phase HPLC. The relative ratios of diasteromers, if any, were compared to see if there is any general trend of racemization, depending on the amino acid(s) and/ or coupling reagents employed.