122 



H. GOBIND KHORANA 



attack of the polymerization reagent (dicyclohexylcarbodiimide or p-tolu- 

 enesulfonyl chloride) on the 3'-hydroxyl function of the nucleotide. Com- 

 parative studies of rates of polymerization using different activating agents 

 should throw light on the mechanism of polymerization itself and on the 

 avoidance of side products. 



In extension of the above work with thy midine-5 '-phosphate, the poly- 

 merization of thymidine-3 '-phosphate has also been carried out and has 

 furnished moderate amounts of the expected new series of linear thymidine 

 oligonucleotides which bear 3'-phosphomonoester groups at one end and 

 5'-hydroxyl groups at the other. 



b. Other Deoxyribo-oligonacleotides 



The principle of adding a protected nucleotide, which can serve only as 

 an activated phosphate donor, to a different free nucleotide can be utilized 

 to obtain useful series of compounds, namely, homopolymers terminated in 

 a different nucleotide at one of the ends. Thus copolymerization of N ,0- 

 diacetyldeoxycytidine-5'-phosphate and thymidine-5'-phosphate, followed 

 by alkaline treatment, yielded linear thymidine oligonucleotides, each bear- 

 ing a terminal deoxycy tidy lie acid residue. 25 ' 26 



In investigation of the polymerization of other deoxyribonucleoside-5'- 

 phosphates, serious interference was encountered from the amino groups 

 on the heterocyclic rings of these compounds. Methods have recently been 

 devised for the preparation in virtually quantitative yields of the protected 

 deoxyribonucleot ides, A7 6 -benzoyl and A^-anisyldeoxycytidine-S'-phosphates 

 (XXXVIII) 26a and A^ 6 -benzoyldeoxyadenosine-5'-phosphate (XXXIX) . 26b 

 Their polymerization by the methods discussed above, followed by removal 

 of the iV-acyl groups by treatment with ammonia gave, respectively, deoxy- 

 cy tidine and deoxyadenosine oligonucleotides. The homologous linear oligo- 

 nucleotides of both series were shown to contain the typical C 3 '-C 5 ' inter- 

 nucleotide bonds. 



R— NH R— NH 



N 



S 



^\ 



S 



C) 



HO- 



O 



-POCH2, 

 OH 







OH H 



(XXXVIII) 

 R = Benzoyl or anisyl 



OH 



(XXXIX) 

 R = Benzoyl 



H 



26tt H. G. Khorana, A. F. Turner, and J. P. Vizsolyi, /. Am. Chem. Soc. in press. 

 26b R. K. Ralph and H. G. Khorana, J. Am. Chem. Soc. in press. 



