A GENTLE METHOD FOR LINKING TRIS TO AMINO-ACIDS AND PEPTIDES

A gentle method for the addition of Tris to the carboxyl group of amin o acids or peptides for the purpose of altering their solubility and/o r for providing sites for further derivatization is described. Under m ild alkaline conditions and in high concentrations of aqueous dimethyl formamide, the amino group of Tris cleaves simple esters of N-protecte d amino acids or peptides to form an amino acid-Tris linkage. The effe cts of pH, temperature and dimethylformamide concentration on the rate and the efficiency of the reaction of Tris with benzyloxycarbonyl-ala nine methyl ester were examined and the general applicability of the m ethod demonstrated on a range of amino acid and small peptide substrat es. Side-chain protection was not required and the degree of racemizat ion was found to be lower than with conventional chemical coupling.