Reference: PD 12110
Technical Field:
Research Tool: Chemical Reagent
Background:
In amide-forming reactions with R-amino acids, the use of a coupling additive such as benzotriazole derivatives [e.g., 1-hydroxy-7-azabenzotriazole (HOAt) and hydroxybenzotriazole (HOBt)] is essential to suppress racemization and improve the efficacy of peptide synthesis.
Oxyma, ethyl 2-cyano-2-(hydroxyimino) acetate, is considered an excellent nonexplosive replacement for HOBt and HOAt. Effectiveness in suppressing racemization and increasing the reaction rate of peptide-forming reactions using Oxyma are believed to be similar to those of HOBt. To date, several attractive features of Oxyma in peptide chemistry have been reported using a conventional organic solvent such as DMF.
The unmet need: Although amide bond-forming reactions can often be performed in water containing organic solvents, no practical peptide coupling additive has been developed for the synthesis of oligopeptides in water.
The Technology Solution:
UTHSC researchers have developed a new Oxyma derivative which displays remarkable physicochemical properties as a peptide-coupling additive in water media. Short peptides as well as oligopeptides could be synthesized by using the Oxyma derivative, EDCI, and NaHCO3 in water without measurable racemization products. Significantly, simple basic and acidic aqueous workup procedures can remove all reagents utilized in the reactions to afford coupling products in high yield with excellent purity. In addition, the Oxyma derivative displayed a remarkable effect on selective esterifications of primary alcohols.
Benefits
Recent publications of the technology:
Patents:
• PCT/US2013/031863
The Inventor:
Dr. Michio Kurosu joined the UT College of Pharmacy faculty in January 2011 as an Associate Professor in the Department of Pharmaceutical Sciences. His research focuses on medicinal chemistry and synthetic organic chemistry involving compounds to treat drug-resistant pathogens, novel cancer chemotherapies, and biologically active natural products. Dr. Kurosu received his PhD in 1995 from the College of Pharmaceutical Sciences at Osaka University in Japan. Prior to joining UT, he was a faculty member at Colorado State University.