Synthese des immunspezifischen, polypeptid-artigen haptens der anthrax-subtilis bacillengruppe. Ein synthetischer beweis der konstitution der natürlichen polyglutaminsäuren

Abstract

γ-Poly- l-glutamic acid (IIIa), γ-poly- d-glutamic acid (IIIb) and mesoid γ-poly-glutamic acid (IIIc) have been synthesised. The syntheses started from αα′-dimethyl γ-glutamyl-glutamate of either the l- l-form (Ia) or the d- d-form or the l- d-form, respectively, prepared from the corresponding glutamic acid stereoisomer in a series of consecutive steps. The directed intermolecular polyacylation of these bifunctional dipeptides to α-methyl γ-polyglutamates (II) of the respective configuration has been effected by activation either of the carboxyl or of the amino group, in altogether four different ways. The polyester so forming has then been hydrolysed with aqueous alkali, and the polyacid—isolated in form of its copper (II) salt—was purified after foregoing demetalation by carefully conducted dialysis. The synthetic stereoisomers of γ-poly-glutamic acid have then been compared with the anthrax polypeptide and subtilis polypeptide. The γ-poly- d-glutamic acid proved to be identical in any respect with the anthrax polypeptide, and was found (by Prof. G. Ivánovicx) to give a precipitation reaction with antianthrax horse immune serum. Since the mesoid γ-poly-glutamic acid was likewise found to produce a precipitate in this reaction it appears that the subtilis polypeptide may contain peptide chains composed of units of both the l- and the d-form of glutamic acid. The synthesis of γ-poly- d-glutamic acid (=anthrax polypeptide) represents the first total synthesis of a natural hapten.