Several structural motifs cooperate in determining the highly effective anti-thrombin activity of NU172 aptamer.
Several structural motifs cooperate in determining the highly effective anti-thrombin activity of NU172 aptamer.
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DOI：
10.1093/nar/gky990
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发表时间：
2018-12-14
影响因子：
14.9
通讯作者：
Sica F
中科院分区：
文献类型：
--
作者：
Troisi R;Napolitano V;Spiridonova V;Russo Krauss I;Sica F
Despite aptamers are very promising alternative to antibodies, very few of them are under clinical trials or are used as drugs. Among them, NU172 is currently in Phase II as anticoagulant in heart disease treatments. It inhibits thrombin activity much more effectively than TBA, the best-known thrombin binding aptamer. The crystal structure of thrombin-NU172 complex reveals a bimodular duplex/quadruplex architecture for the aptamer, which binds thrombin exosite I through a highly complementary surface involving all three loops of the G-quadruplex module. Although the duplex domain does not interact directly with thrombin, the features of the duplex/quadruplex junction and the solution data on two newly designed NU172 mutants indicate that the duplex moiety is important for the optimization of the protein-ligand interaction and for the inhibition of the enzyme activity. Our work discloses the structural features determining the inhibition of thrombin by NU172 and put the basis for the design of mutants with improved properties.
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DOI：
10.1107/s090744491003982x
发表时间：
2011-04
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Evans PR
通讯作者：
Evans PR
影响因子：
14.9
作者：
Dolot R;Lam CH;Sierant M;Zhao Q;Liu FW;Nawrot B;Egli M;Yang X
通讯作者：
Yang X
影响因子：
10.4
作者：
Chan, M. Y.;Rusconi, C. P.;Becker, R. C.
通讯作者：
Becker, R. C.
影响因子：
10.4
作者：
Crawley, J. T. B.;Zanardelli, S.;Lane, D. A.
通讯作者：
Lane, D. A.
影响因子：
37.8
作者：
Chan, Mark Y.;Cohen, Mauricio G.;Rusconi, Christopher P.
通讯作者：
Rusconi, Christopher P.