Inhibition of (cytosine C5)-methyltransferase by oligonucleotides containing flexible (cyclopentane) and conformationally constrained (bicyclo[3.1.0]hexane) abasic sites |
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| Authors: | Marquez V E Wang P Nicklaus M C Maier M Manoharan M Christman J K Banavali N K Mackerell A D |
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| Affiliation: | Laboratory of Medicinal Chemistry, Division of Basic Sciences, NCI-FCRDC, Boyles St., Bldg. 376, Frederick, Maryland 21702, USA. |
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| Abstract: | Pseudorotationally locked sugar analogues based on bicyclo[3.1.0]-hexane templates were placed in DNA duplexes as abasic target sites in the M. HhaI recognition sequence. The binding affinity of the enzyme increases when the abasic site is constrained to the South conformation and decreases when it is constrained to the North conformation. A structural understanding of these differences is provided. |
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