A comparative conformational study of thymidylyl(3'----5')-thymidine, thymidylyl(3'----5')-5'-thio-5'- deoxythymidine and thymidinylacetamido-[3'(O)----5'(C)]-5'-deoxythymidine.
A comparative 270 MHz NMR spectroscopic study on the solution structure of the dimer d(TpT) 1, and its two analogues, namely, d(TpST) 2, and NH2d(TcmT) 4 has been reported. Analysis of chemical shifts and coupling constants indicate that: (i) The sugar moieties of the constituent nucleotides are not affected by modification of the internucleotide linkages and adopt preferentially an S-type conformation. (ii) The C4'-C5' bond in the pT part of the modified dimers 2 and 4 shows a large conformational freedom (gamma+ = 32% and 35%, respectively) compared to 1 (gamma+ = 75%). (iii) The population of the trans conformer about C5'-O5' is less important in d(TpST) 2 compared to d(TpT) 1. (iv) The C3'-O3' bond in 2 adopts a trans conformation as in 1. (v) The glycosidic bonds in the modified dimers 2 and 4 showed preferential syn conformation. UV and CD data show that the modified dimers 2 and 4 have poor tendency to stack intramolecularly, they also base pair less efficiently with d(ApA) as compared to d(TpT) 1.
Glemarec
C
C
Department of Bioorganic Chemistry, University of Uppsala, Sweden.
Nyilas
A
A
Sund
C
C
Chattopadhyaya
J
J
D002236:Carbohydrate Conformation; D002942:Circular Dichroism; D015226:Dinucleoside Phosphates / Q000138:chemical synthesis* / Q000737:chemistry*; D006027:Glycosides / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008956:Models, Chemical; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D010758:Phosphorus / Q000737:chemistry; D011522:Protons; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature
D015226:Dinucleoside Phosphates; D006027:Glycosides; D011522:Protons; C068421:thymidylylacetamido-(3'(O)-5'(C))-5'-deoxythymidine; C017758:thymidylyl-(3'-5')-thymidine; D010758:Phosphorus; C068420:thymidylyl(3'-5')-5'-thio-5'-deoxythymidine