106 GENERAL BIOCHEMISTRY 



CHsOCONHCHRCONHCHR'COO- „^ p^ 



> 



I + CO. + HsN+CHRCONHCHR'COO- 



When the appropriate groups have been protected, one of several 

 available methods of activation is applied to bring about the forma- 

 tion of the peptide bond. Three procedures are cited as examples, 

 with R" and R"' representing protecting groups that are removed 

 later. 



R"NHCHRCOOH "^ R"NHCHRCOCl ^l^^^^^S^ 



R"NHCHRCONHGHR'COOR'" 



H'-NNHj , HNO2 



R"NHCHRCOOEt > R^NHCHRCOHNNH. > 



R"NHCHRCON3 



HsNCHR'COOR'" 



R"NHCHRCONHGHR'COOR"' + HN3 

 NH2CHRCOOR'" + (EtO)2POP(OEt)2 ^^^°^'^"" 



tetraethyl- diethyl- 



pyrophosphite phosphite 



(EtO)2PNHCHRCOOR'" + (EtO)2POH 



R"NHCHRCOOH 



R"NHCHRCONHCHR'GOOR"' + (EtO)2POH 



Of these, the first two procedures represent activation of the carboxyl 

 group and the last method represents activation of the amino group. 

 The last reaction can be used to activate the carboxyl group instead of 

 the amino group if the tetraethylpyrophosphite is added to the N-acyl- 

 amino acid derivative first. Many other methods have been used. 

 Some have general utility; some can be applied only to the synthesis 

 of particular peptides. A wide variety of protecting and activating 

 methods is necessary in view of the diversity of the amino acids in- 

 volved and the differences in their chemical properties. 



Occurrence 



It is theoretically possible to combine the rather sizable number of 

 naturally occurring amino acids into an enormous variety of peptides 

 differing in size, composition, or the sequence of the component amino 

 acids. It is probable that the number of peptides occurring naturally 

 in free form is large. However, methods of isolation, separation, and 



