The Development of a Plasma Volume Expander 59 



obtained of such degree of purity and homogeneity that they are 

 acceptable in many respects, prolonged trial has nevertheless demon 

 strated certain unsatisfactory properties such as antigenicity and un- 

 desirable prolongation of bleeding time due to an unknown effect on 

 the hemostatic mechanism. 



A third class of substances, of which there is one outstanding repre- 

 sentative, is that of the synthetic polymers. The polymer of vinyl 

 pyrrolidine known as PVP was used extensively by the Germans in 

 World War II, with considerable success. It has been used to some 

 extent in this country but is felt to be undesirable because the material 

 is taken up by the reticuloendothelial system and remains there 

 indefinitely. 



Against this background attention can now be turned to the exami- 

 nation of another substance or group of substances which have been 

 proposed and which offer some uniquely interesting properties with 

 reference to their use as plasma volume expanders. These are the 

 peptides of glutamic acid and polymers of these peptides. These 

 polymers of glutamic acid can be produced both synthetically and 

 biologically, but the biologically produced material will receive major 

 consideration here. 



Glutamyl polypeptide was first described and isolated by Ivanovics 

 and Erdos, 1 who observed that it was a component of the capsule of 

 Bacillus anthrads and of Bacillus subtilis. These investigators, who 

 first isolated the pure polypeptide, demonstrated that it was composed 

 of glutamic acid residues linked in y linkage. 



Oui' interest in this material first arose in connection with the pos- 

 sibility that this peptide might offer an opportunity of studying the 

 enzymatic synthesis of the peptide linkage. The reason for this was 

 twofold. The peptide was formed as an extracellular product in 

 B. subtilis cultures, and it was hoped that a cell-free synthetic enzyme 

 system might be obtained similar to the system successfully studied 

 by Hehre - in the dextran-producing organism Leuconostoc mesen- 

 teroides. Furthermore, it was felt that, since the peptide contained 

 only one amino acid, the enzyme system involved in its biosynthesis 

 might be less complex than those needed for other peptide syntheses, 

 and thus offer a favorable starting point for attack on the general 

 problem of peptide biosynthesis. 



It was first necessary to demonstrate that the material obtained 

 from the strains we worked with was truly composed of only glutamic 

 acid and to ascertain the nature of the peptide linkage. Fortunately 

 for the purposes of both these experiments and subsequent develop- 



