66 



Essays in Biochemistry 



strate that mere increase in molecular length of peptide is not in itself 

 sufficient to effect significant changes in length of retention in the blood 

 stream of humans. Thus, increasing the size of the straight glutamyl 

 peptide chain from 10,000 to 120,000, a twelvefold increase in length, 

 gives no real increase in the blood-stream half-life, which is approxi- 

 mately 1 hour for both, even though the large molecules are now many 

 times the length of the serum albumin molecules. As can be seen in 

 Fig. 1 the large peptide is excreted with almost the same rapidity 



o Dog 2.4 gm. peptide infused, mol. wt. 56,000 

 • Man 20 gm. peptide infused, mol. wt. 120,000 

 X Man 3 gm. peptide infused, mol. wt. 15,000 



10 12 



Hours post infusion 



Fig. 1. Plasma levels of straight chain peptide in man and dog. 



as is the small. A conjugate with molecular weight of the order of 

 120,000, having side chains with molecular weights of approximately 

 8000, shows a half-life at least 10 times that of straight-chain peptide 

 of the same molecular weight. 



Strangely enough, the situation is different in dogs. In this animal 

 straight-chain peptides of molecular weights of 60,000 and over have 

 a half-life in the blood stream of 12 hours or longer and bring about 

 the desired hemodilution while in the blood stream. This difference 

 between the two species is of considerable practical interest as the dog 

 is the most commonly used test animal for plasma volume extender 

 tests. In this case, at least, the results with the dog w r ere entirely 

 misleading with respect to behavior of the straight-chain peptide in 

 man. Whether or not this difference between humans and dogs relates 

 to differences in kidney physiology or in the manner in which the 

 peptide is metabolized in the two species has not yet been ascertained. 



It was quite evident in view of the above results that the investiga- 

 tions of conjugates and polymers of glutamyl peptide must be resumed. 



