International Journal of Peptide and Protein Reseach 1985-09-01

Semisynthesis of linear gramicidins using diphenyl phosphorazidate (DPPA).

L B Weiss, R E Koeppe

Index: Int. J. Pept. Protein Res. 26(3) , 305-10, (1985)

Full Text: HTML

Abstract

Sequential HPLC analysis has been used to optimize a synthetic scheme for the preparation of semisynthetic position 1 analogues of the channel-forming pentadecapeptide, gramicidin A. Diphenyl phosphorazidate (DPPA) was more efficient than dicyclohexylcarbodiimide (DCC) for the coupling of N-formyl amino acids to des(formyl-valyl) gramicidin A. The DPPA coupling proceeds rapidly, and with high yield, at 0 degree. The absence of significant (less than 0.1%) racemization is demonstrated by the lack of electrophysiologically active formyl-L-valine gramicidin A in preparations of formyl-D-valine gramicidin A. This scheme has proved useful for the preparation of microgram to gram amounts of position-1-substituted gramicidin analogues suitable for crystallography and electrophysiology. Details of the techniques for the preparation of these highly purified analogues are discussed.