2-Thiozebularine: base modified nucleoside fully constrained in C3′-endo conformation in solution

[img]PDF - Authorized users only
Language: English
697Kb
Title:2-Thiozebularine: base modified nucleoside fully constrained in C3′-endo conformation in solution
Creators:
Ebenryter, Katarzyna
Jankowski, Stefan
Karolak-Wojciechowska, Janina
Fruziński, Andrzej
Kaźmierczak-Baranska, Julia
Nawrot, Barbara
Sochacka, Elzbieta
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 76, 9, pp. 1103-1119
Uncontrolled Keywords:X-ray, Zebularine, Conformation of nucleosides, Cytotoxity of nucleosides, Modified nucleosides, 2-Thiozebularine, NMR

Abstract

2-Thiopyrimidinone ribofuranoside (2-thiozebularine, s<sup>2</sup>zeb) was synthesized by the adaptation of silyl method of N-glycosidic bond formation and using thionation of protected 2-oxonucleoside derivative (zebularine, zeb) with Lawesson reagent. The X-ray crystal structure of s<sup>2</sup>zeb and NMR determined conformations of s<sup>2</sup>zeb and zeb in solution were compared with structures of 2-thiouridine (s<sup>2</sup>U) and uridine (U). In the solid state s<sup>2</sup>zeb molecule adopts conformation typical for ribonucleosides: C3′-<i>endo</i> C2′-<i>exo</i> twist type of ribofuranose pucker, <i>anti</i> of N-glycosidic bond and <i>trans</i> around C4′–C5′ bond. In aqueous solution, however, almost 100% population of s<sup>2</sup>zeb exhibits C3′-<i>endo</i> ribofuranose pucker. The population of N-conformer of s<sup>2</sup>zeb is about 20% higher than for zeb (analogously to pair of s<sup>2</sup>U and U nucleosides) indicating similar influence of steric effect of bulky sulfur atom on stabilization of N-type ribose conformation. Interestingly, the absence of 4-carbonyl function in zeb and s<sup>2</sup>zeb raises the population of C3′-<i>endo</i> conformation by about 30% in comparison to U and s<sup>2</sup>U as a result of significant anomeric effect. Additive action of both effects makes the 2-thiozebularine almost fully constrained in C3′-<i>endo</i> conformation in aqueous solution. Cytotoxic properties of s<sup>2</sup>zeb are less pronounced in comparison to zebularine, with IC<sub>50</sub> > 100 mM for HeLa and K562 cancer cells and for HUVEC non-cancerous cells.

Title:2-Thiozebularine: base modified nucleoside fully constrained in C3′-endo conformation in solution
Creators:
Ebenryter, Katarzyna
Jankowski, Stefan
Karolak-Wojciechowska, Janina
Fruziński, Andrzej
Kaźmierczak-Baranska, Julia
Nawrot, Barbara
Sochacka, Elzbieta
Uncontrolled Keywords:X-ray, Zebularine, Conformation of nucleosides, Cytotoxity of nucleosides, Modified nucleosides, 2-Thiozebularine, NMR
Divisions:Life and Chemical Sciences > Institute of Organic Chemistry and Biochemistry > Collection of Czechoslovak Chemical Communications
Journal or Publication Title:Collection of Czechoslovak Chemical Communications
Volume:76
Number:9
Page Range:pp. 1103-1119
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc2011081UNSPECIFIED
ID Code:6778
Item Type:Article
Deposited On:01 Sep 2011 12:57
Last Modified:01 Sep 2011 10:57

Citation

Ebenryter, Katarzyna; Jankowski, Stefan; Karolak-Wojciechowska, Janina; Fruziński, Andrzej; Kaźmierczak-Baranska, Julia; Nawrot, Barbara; Sochacka, Elzbieta (2011) 2-Thiozebularine: base modified nucleoside fully constrained in C3′-endo conformation in solution. Collection of Czechoslovak Chemical Communications, 76 (9). pp. 1103-1119.

Repository Staff Only: item control page