Novel bimodular DNA aptamers with guanosine quadruplexes inhibit phylogenetically diverse HIV-1 reverse transcriptases.
Novel bimodular DNA aptamers with guanosine quadruplexes inhibit phylogenetically diverse HIV-1 reverse transcriptases.
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具有鸟苷四链体的新型双模块 DNA 适体可抑制系统发育多样化的 HIV-1 逆转录酶。
DOI:
10.1093/nar/gkn891
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发表时间:
2008-12
影响因子:
14.9
通讯作者:
Burke, Donald H.
中科院分区:
文献类型:
--
作者:
Michalowski, Daniel;Chitima-Matsiga, Rebecca;Held, Daniel M.;Burke, Donald H.
DNA aptamers RT5, RT6 and RT47 form a group of related sequences that inhibit HIV-1 reverse transcriptase (RT). The essential inhibitory structure is identified here as bimodular, with a 5′ stem–loop module physically connected to a 3′-guanosine quadruplex module. The stem–loop tolerates considerable sequence plasticity. Connections between the guanosine triplets in the quadruplex could be simplified to a single nucleotide or a nonnucleic acid linker, such as hexaethylene glycol. All 12 quadruplex guanosines are required in an aptamer retaining most of the original loop sequence from RT6; only 11 are required for aptamer R1T (single T residue in intra-quadruplex loops). Circular dichroism (CD) spectroscopy gave ellipticity minima and maxima at 240 nm and 264 nm, indicating a parallel arrangement of the quadruplex strands. The simplified aptamers displayed increased overall stability. An aptamer carrying the original intra-quadruplex loops from RT6 inhibited RT in K+ buffers but not in Na+ buffers and displayed significant CD spectral broadening in Na+ buffers, while R1T inhibited RT in both buffers and displayed less broadening in Na+ buffers. The bimodular ssDNA aptamers inhibited RT from diverse primate lentiviruses with low nM IC50 values. These data provide insight into the requirements for broad-spectrum RT inhibition by nucleic acid aptamers.
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DOI:
10.1073/pnas.90.13.6320
发表时间:
1993-07-01
影响因子:
11.1
作者:
JACOBOMOLINA, A;DING, JP;ARNOLD, E
通讯作者:
ARNOLD, E
影响因子:
2.9
作者:
Andreola, ML;Pileur, F;Litvak, S
通讯作者:
Litvak, S
影响因子:
4.8
作者:
Etzioni, S;Yafe, A;Fry, M
通讯作者:
Fry, M
影响因子:
2.2
作者:
Fisher, Timothy S;Joshi, Pheroze;Prasad, Vinayaka R
通讯作者:
Prasad, Vinayaka R
影响因子:
4.8
作者:
Held, Daniel M.;Kissel, Jay D.;Burke, Donald H.
通讯作者:
Burke, Donald H.