Abstract
Impact of saturation of the sugar C(3’)=C(4’) bond of acytidine nucleoside derivative, 3’, 4’-didehydro-3’-deoxycytidine (I) is revealed usingsimulated vibrational spectra, with respect to 3’-deoxycytidine. The density functional theory based calculations found that the C(3’)=C(4’) double bondrestricts the sugar flexibility and affects the sugar-base intramolecular hydrogen bond network. For 3’-dC, two minimal energy conformers are identified on the potential energy surface. The first conformer (IIA) takes anO4’-endo and gauche-gauche (gg) orientation whereas the second (IIB) has a C3’-exo and gauche-trans (gt) orientation in gas phase. The two conformers which have been observed previously in the crystal structure are separated by a low energy barrier. The carbon double bond in the sugar moiety of I confines the pseudorotation of the pentagon ring to be significantly flatter than that of the sugar ring in IIA and IIB. The simulated vibrational spectra, both in gas phase and in solutions, report such structural caused spectral changes with red and blue vibrational frequency shifts.The firsthydration shell of 3’-dC has been also investigated applying hybrid QM/MM molecular dynamic simulation.
Highlights
Cytidine analogues are an important class of chemotherapeutic agents used mainly as anti-tumoror anti-viralagents(Galmarini, Jordheim, & Dumontet, 2003; Schinazi et al, 2002)
Studying geometrical properties of nucleosides and their analogues is important, as this may affect the interactions with their macromolecular targets (Harte Jr. et al, 1991; Choi et al, 2003)
As commonly observed in most pyrimidine nucleosides and their analogues, the minimal structures are generally belonging to the anti category of conformation, which refers to the orientation of the sugar ring relative to the base moiety, and is defined by the angle (= O(4′)-C(1′)-N(1)-C(2)).The Potential Energy Surface (PES) of each nucleoside has been explored for other conformational structures that may be populated
Summary
Cytidine analogues are an important class of chemotherapeutic agents used mainly as anti-tumoror anti-viralagents(Galmarini, Jordheim, & Dumontet, 2003; Schinazi et al, 2002). Previous studies have reported that anti-HIV activity of the nucleoside antibiotics drugs depends upon the ribose conformer (Torrance et al, 2001), usually with an unsaturated sugar ring and lack of the C2’-OH or C3’-OH groups.It has been shown that conformational changes may impact the anti-viral or the anti-tumor activity (Rodriguez et al, 1994; Wang, 2000). II is known to be an www.ccsenet.org/ijc
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