Synthesis and enzymatic hydrolysis of glutamic acid polypeptides.

Synthetic lysine polypeptides of high molecular weight (1) have been shown to reduce virus infectivity (2, 3), inhibit bacterial growth and respiration (4), agglutinate virus particles, bacterial cells, and erythrocytes (4-6), and to prolong blood clotting time (7). It has been suggested that most of these phenomena are associated with the formation of many ionic bonds between the positively charged lysine polypeptide and the appropriate negatively charged receptors on the virus particles, bacterial or red blood cells. In view of the above effects produced by the basic lysine polypeptides it was of interest to synthesize high molecular weight acidic glutamic acid polypeptides and to study their biological effects. This paper presents the synthesis and properties of L-glutamic acid polypeptides and their susceptibility to hydrolysis by proteolytic enzymes. When this work was undertaken, the only published reference to synthetic glutamic acid polypeptides was a brief report by Hanby et al. (8). Subsequently and during the course of this work a more complete description of the synthesis of glutamic acid polypeptides was published by the same authors (9) and also by Coleman (10). Although the synthesis described in this paper is somewhat similar to that reported by these authors, it differs in the method used to prepare the N-carboxy anhydride, in the technique of polymerization which allows control of the polypeptide size, and in the method for hydrolysis of polyglutamic ethyl ester which avoids racemization and gives an analytically pure polyglutamic acid. synthesis-Polyglutamic acid was prepared by polymerization of N-carboxy y-ethyl-L-glutamate anhydride which was synthesized as shown by structures I to V. The polymerization, which was carried out in dry dioxane at room temperature with varying amounts of anhydrous ammonia as initiator (l), yielded polypeptide preparations of different average molecular weights. The results are consistent with the polymerization scheme (V to VIII).