Contribution to the Elucidation of the Chemical Structure of Polymyxin B1*

Abstract

In order to determine the total structure, polymyxin B₁ has been enzymatically hydrolyzed with Subtilopeptidase A and the resulting hydrolvsate was fractionated by countercurrent distribution. Four peptides have been isolated and their amino acid sequences were determined, and the peptides, MOA→(α)L-DAB→L-Thr→(α)L-DAB and cyclo-(γ)L-DAB→(α)L-DAB→D-Phe→L-Leu→(α)L-DAB→(α)L-DAB→L-Thr→, which were essential to elucidate the full structure of polymyxin B were obtained. It was thus determined that the side chain is linked to the α-amino group of an α, γ-diaminobutyric acid residue in the cyclic peptide portion and the γ-amino group of this residue is involved in the ring formation, and that the amino acids present in polymyxin B₁ are contained as the L-configuration except phenylalanine. The structure of polymyxin B₁ was thus elucidated to be MOA→(α)L-DAB→L-Thr→(α)L-DAB→cyclo-(γ)L-DAB→(α)L-DAB→D-Phe→L-Leu→(α)L-DAB→(α)L-DAB→L-Thr→.