The effect on quadruplex stability of North-nucleoside derivatives in the loops of the thrombin-binding aptamer

被引：16

作者：

Avino, Anna ^{[1
,2
]}

Mazzini, Stefania ^{[3
]}

Ferreira, Ruben ^{[1
,2
]}

Gargallo, Raimundo ^{[4
]}

Marquez, Victor E. ^{[5
]}

Eritja, Ramon ^{[1
,2
]}

机构：

[1] CSIC, Inst Res Biomed IRB Barcelona, Networking Ctr Bioengn Biomat & Nanomed CIBER BBN, E-08028 Barcelona, Spain

[2] CSIC, Inst Adv Chem Catalonia IQAC, E-08028 Barcelona, Spain

[3] Univ Milan, Dipartimento Sci Mol Agroalimentari, I-20133 Milan, Italy

[4] Univ Barcelona, Dept Analyt Chem, E-08028 Barcelona, Spain

[5] NCI, Biol Chem Lab, Ctr Canc Res, Ft Detrick, MD 21702 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2012年 / 20卷 / 14期

关键词：

Quadruplex; Thrombin-binding aptamer; NMR; Oligonucleotide synthesis; Uridine; 2 '-Deoxy-2 '-fluorouridine; North-methanocarbathymidine; TELOMERIC G-QUADRUPLEX; INTRAMOLECULAR G-QUADRUPLEX; SINGLE-BASE LOOPS; DNA APTAMER; NUCLEIC-ACID; SUGAR PUCKER; SEQUENCE; TOPOLOGY; CONFORMATIONS; DETERMINES;

D O I：

10.1016/j.bmc.2012.06.005

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Modified thrombin-binding aptamers (TBAs) carrying uridine (U), 2'-deoxy-2'-fluorouridine (FU) and North-methanocarbathymidine (NT) residues in the loop regions were synthesized and analyzed by UV thermal denaturation experiments and CD spectroscopy. The replacement of thymidines in the TGT loop by U and FU results in an increased stability of the antiparallel quadruplex structure described for the TBA while the presence of NT residues in the same positions destabilizes the antiparallel structure. The substitution of the thymidines in the TT loops for U, FU and NT induce a destabilization of the antiparallel quadruplex, indicating the crucial role of these positions. NMR studies on TBAs modified with uridines at the TGT loop also confirm the presence of the antiparallel quadruplex structure. Nevertheless, replacement of two Ts in the TT loops by uridine gives a more complex scenario in which the antiparallel quadruplex structure is present along with other partially unfolded species or aggregates. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：4186 / 4193

页数：8

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