Conformations of Cyclobut-A and Cyclobut-G: structural resemblance to nucleosides and incorporation into double helical DNA.
Conformational energy calculations have been carried out on two modified nucleosides Cyclobut-A and Cyclobut-G using the methods of molecular mechanics (MM2) obtainable in the computational software MacroModel. Conformations were generated as a function of the torsion angles equivalent to the glycosidic and backbone torsions in deoxyribonucleotides. The structural resemblance of the energy minimized models of the modified nucleosides to their corresponding deoxyribonucleosides has been investigated. It is found that conformations which lie within 3 kcal/mole of the global minimum do resemble the overall shape and volume of the B-DNA nucleoside. Following this result, two deoxypentanucleotides d(GCGCG).d(CGCGC) and d(ATATA).d(TATAT) were model built incorporating cyclobut-G and cyclobut-A, respectively. These were then energy refined using the molecular mechanics package AMBER. The resultant structures demonstrate that cyclobut-A and cyclobut-G can be easily accommodated in double helical polynucleotides with minimal overall distortions.
Rao
S N
SN
Searle Research and Development, Skokie, IL 60077.
D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry; D000998:Antiviral Agents / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D003853:Deoxyribonucleosides / Q000737:chemistry*; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry; D008958:Models, Molecular; D009690:Nucleic Acid Conformation
D000998:Antiviral Agents; D003853:Deoxyribonucleosides; C062353:cyclobut A; D006147:Guanine; C063638:lobucavir; D004247:DNA; D000225:Adenine