PROTEINS 



105 



The synthesis of pcplidcs by cells is the subject of imuli cuiicnt 

 study, but the iiiechanisms have not yet been established. However, 

 laboratory syntheses have been developed and many peptides are now 

 available. The method employed in any given case depends primarily 

 on three factors. First, one of the reacting structures, either the carboxy- 

 late or ammonium ion, must be activated by modifying it in some 

 way. Second, reaction of the activated molecule with another of its 

 own kind must be prevented. Finally, any additional functional 

 groups of the amino acids involved must be preserved. The last con- 

 dition is usually met by protecting these additional structures with 

 groups that can be removed later or by choosing a method of activa- 

 tion that does not lead to reaction of the auxiliary structures. 



Reaction of activated amino acid molecules with themselves instead 

 of with the second kind of amino acid is always a problem. The diffi- 

 culty arises, of course, because both structures participating in pep- 

 tide-bond formation occur in each component molecule. The prob- 

 lem is met in one of two ways. The original reactants may not both 

 be amino acids but may be derivatives forming amides later converted 

 to peptides, as with 



ClCHRCOCl 4- HaN+CHR'COO 

 CICHRCONHCHR'COO- 



^^^ HsN+CHRCONHGHR'COO- 



where R and R' stand for any of the side groups typical of amino 

 acids. Often the necessary chloro acids are not available. Then it is 

 usual to protect either the ammonium or carboxylate structure with a 

 group that can be removed later. In the latter case, simple esters are 

 usually made. A number of protecting groups are used to cover the 

 ammonium ion, most of them forming complex amides as in 



/-^CH.20H 



^^^ 



benzyl 

 alcohol 



+ COCI2 



phosgene 



^.^^CHsOGOCl jj 



3N+CTIRC00- 



"^^ 



carbol)eiizyloxy 

 cliloride 



/^^CHoOCONHCHRCOO- 



After this derivative has been coupled to a second amino acid, the 

 protecting group may be removed by reduction, giving the peptide in 

 high yield. 



LIBRARY |5?| 



