scholarly journals Improved Thermodynamic Parameters and Helix Initiation Factor to Predict Stability of DNA Duplexes

1996 ◽  
Vol 24 (22) ◽  
pp. 4501-4505 ◽  
Author(s):  
Naoki Sugimoto ◽  
Shu-ich Nakano ◽  
Mari Yoneyama ◽  
Kei-ich Honda

Abstract To improve the previous DNA/DNA nearest-neighbor parameters, thermodynamic parameters (Δ H °, Δ S ° and Δ G °) of 50 DNA/DNA duplexes were measured. Enthalpy change of a helix initiation factor is also considered though the parameters reported recently did not contain the factor. A helix initiation factor for DNA/DNA duplex determined here was the same as that of RNA/RNA duplex (ΔG° 37 = 3.4 kcal/mol). The improved nearest-neighbor parameters reproduced not only these 50 experimental values used here but also 15 other experimental values obtained in different studies. Comparing Δ G ° 37 values of DNA/DNA nearest-neighbor parameters obtained here with those of RNA/RNA and RNA/DNA, RNA/RNA duplex was generally the most stable of the three kinds of duplexes with the same nearest-neighbor sequences. Which is more stable between DNA/DNA and RNA/DNA duplexes is sequence dependent.

Biochemistry ◽  
2004 ◽  
Vol 43 (18) ◽  
pp. 5388-5405 ◽  
Author(s):  
Patricia M. McTigue ◽  
Raymond J. Peterson ◽  
Jason D. Kahn

2020 ◽  
Vol 117 (25) ◽  
pp. 14194-14201 ◽  
Author(s):  
Saptarshi Ghosh ◽  
Shuntaro Takahashi ◽  
Tatsuya Ohyama ◽  
Tamaki Endoh ◽  
Hisae Tateishi-Karimata ◽  
...  

The intracellular environment is crowded and heterogeneous. Although the thermodynamic stability of nucleic acid duplexes is predictable in dilute solutions, methods of predicting such stability under specific intracellular conditions are not yet available. We recently showed that the nearest-neighbor model for self-complementary DNA is valid under molecular crowding condition of 40% polyethylene glycol with an average molecular weight of 200 (PEG 200) in 100 mM NaCl. Here, we determined nearest-neighbor parameters for DNA duplex formation under the same crowding condition to predict the thermodynamics of DNA duplexes in the intracellular environment. Preferential hydration of the nucleotides was found to be the key factor for nearest-neighbor parameters in the crowding condition. The determined parameters were shown to predict the thermodynamic parameters (∆H°, ∆S°, and ∆G°37) and melting temperatures (Tm) of the DNA duplexes in the crowding condition with significant accuracy. Moreover, we proposed a general method for predicting the stability of short DNA duplexes in different cosolutes based on the relationship between duplex stability and the water activity of the cosolute solution. The method described herein would be valuable for investigating biological processes that occur under specific intracellular crowded conditions and for the application of DNA-based biotechnologies in crowded environments.


2021 ◽  
Author(s):  
Cyong-Ru Jhan ◽  
Roshan Satange ◽  
Shun-Ching Wang ◽  
Jing-Yi Zeng ◽  
Yih-Chern Horng ◽  
...  

Abstract The use of a small molecule compound to reduce toxic repeat RNA transcripts or their translated aberrant proteins to target repeat-expanded RNA/DNA with a G4C2 motif is a promising strategy to treat C9orf72-linked disorders. In this study, the crystal structures of DNA and RNA–DNA hybrid duplexes with the -GGGCCG- region as a G4C2 repeat motif were solved. Unusual groove widening and sharper bending of the G4C2 DNA duplex A-DNA conformation with B-form characteristics inside was observed. The G4C2 RNA–DNA hybrid duplex adopts a more typical rigid A form structure. Detailed structural analysis revealed that the G4C2 repeat motif of the DNA duplex exhibits a hydration shell and greater flexibility and serves as a ‘hot-spot’ for binding of the anthracene-based nickel complex, NiII(Chro)2 (Chro = Chromomycin A3). In addition to the original GGCC recognition site, NiII(Chro)2 has extended specificity and binds the flanked G:C base pairs of the GGCC core, resulting in minor groove contraction and straightening of the DNA backbone. We have also shown that Chro-metal complexes inhibit neuronal toxicity and suppresses locomotor deficits in a Drosophila model of C9orf72-associated ALS. The approach represents a new direction for drug discovery against ALS and FTD diseases by targeting G4C2 repeat motif DNA.


2015 ◽  
Vol 39 (11) ◽  
pp. 8752-8762 ◽  
Author(s):  
Gaofeng Liu ◽  
Zhiwen Li ◽  
Junfei Zhu ◽  
Yang Liu ◽  
Ying Zhou ◽  
...  

Parallel and anti-parallel T–Hg–T base pairs have different thermal stabilities and conformational influences on DNA duplex structures.


2018 ◽  
Vol 96 (12) ◽  
pp. 1079-1086 ◽  
Author(s):  
Molla R. Islam ◽  
Shakiba Azimi ◽  
Faranak Teimoory ◽  
Glen Loppnow ◽  
Michael J. Serpe

In this investigation, we show that RNA can be separated from a solution containing DNA and RNA and the isolated RNA can be detected using poly (N-isopropylacrylamide-co-N-(3-aminopropyl) methacrylamide hydrochloride) microgel-based optical devices (etalons). The isolation of RNA was accomplished by using hairpin-functionalized magnetic beads (MMPDNA) and differential melting, based on the fact that the DNA–RNA hybrid duplex is stronger (i.e., high melting temperature) than the DNA–DNA duplex (i.e., low melting temperature). By performing concurrent etalon sensing and fluorescent studies, we found that the MMPDNA combined with differential melting was capable of selectively separating RNA from DNA. This selective separation and simple colorimetric detection of RNA from a mixture will help lead to future RNA-based disease diagnostic devices.


1994 ◽  
pp. 335-348
Author(s):  
Thomas L. James ◽  
Karl D. Bishop ◽  
Forrest Blocker ◽  
Carlos Gonzalez ◽  
Anil Kumar ◽  
...  

Biopolymers ◽  
1999 ◽  
Vol 52 (1) ◽  
pp. 29-56 ◽  
Author(s):  
Richard Owczarzy ◽  
Peter M. Vallone ◽  
Robert F. Goldstein ◽  
Albert S. Benight

2013 ◽  
Vol 57 (10) ◽  
pp. 4963-4970 ◽  
Author(s):  
Liang Xu ◽  
Lifeng Cai ◽  
Xueliang Chen ◽  
Xifeng Jiang ◽  
Huihui Chong ◽  
...  

ABSTRACTDiscovery of new drugs for the treatment of AIDS typically possessing unique structures associated with novel mechanisms of action has been of great importance due to the quick drug-resistant mutations of HIV-1 strains. The work presented in this report describes a novel class of DNA duplex-based HIV-1 fusion inhibitors. Hydrophobic groups were introduced into a DNA duplex skeleton either at one end, at both ends, or in the middle. These modified DNA duplexes inhibited fusion between HIV-1 and human cell membranes at micro- or submicromolar concentrations. Respective inhibitors adopted an aptamer pattern instead of a base-pairing interaction pattern. Structure-activity relationship studies of the respective DNA duplexes showed that the rigid and negatively charged DNA skeletons, in addition to the presence of hydrophobic groups, were crucial to the anti-HIV-1 activity of these compounds. A fluorescent resonance energy transfer (FRET)-based inhibitory assay showed that these duplex inhibitors interacted with the primary pocket in the gp41 N-terminal heptad repeat (NHR) instead of interacting with the lipid bilayers.


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