CRYOCHEMISTRY - FREEZING EFFECT ON PEPTIDE COUPLING IN DIFFERENT ORGANIC SOLUTIONS

The freezing effect on peptide coupling in organic solutions of differ ent polarity has been investigated and compared with the results obtai ned in liquid phase. The model reaction of DCC-activated coupling of B oc-Ala-Phe-OH with H-Ala-OBut has been carried out in dioxane, dimethy lsulfoxlde and formamide, as well as in mixtures (90%/10%, v/v) of dio xane with acetonitrile, dimethylformamide, dimethylsulfoxide and forma mide. The reactions have been traced and evaluated by RP-HPLC analysis . Freezing the reaction mixture resulted in all cases in a significant suppression of the N-dipeptidylurea side-product formation together w ith a slight decrease of tripeptide epimerization. The coupling yields and the side effects depended on the solvent, with the dioxane and di oxane/acetonitrile mixture produced the best results. The role of free zing and solvent in the improved results is discussed. (C) 1998 Europe an Peptide Society and John Wiley & Sons, Ltd.