Targeting nucleic acids with a G-triplex-to-G-quadruplex transformation and stabilization using a peptide–PNA G-tract conjugate

2020 ◽  
Vol 56 (48) ◽  
pp. 6567-6570
Author(s):  
Cui-jiao Wen ◽  
Jia-yuan Gong ◽  
Ke-wei Zheng ◽  
Yi-de He ◽  
Jia-yu Zhang ◽  
...  
Keyword(s):  
Nucleic Acids ◽  
Dna Metabolism ◽  
G Quadruplex ◽  
Selective Interference ◽  
Functional Peptide

The synergy between two recognizing units in a bi-functional peptide–PNA G-tract conjugate recognizes a three guanine-tracts motif to form an extra stable bimolecular complex, resulting in highly potent and selective interference to DNA metabolism.

scholarly journals Encapsulation and Ultrasound-Triggered Release of G-Quadruplex DNA in Multilayer Hydrogel Microcapsules

Polymers ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1342 ◽  
Author(s):  
Aaron Alford ◽  
Brenna Tucker ◽  
Veronika Kozlovskaya ◽  
Jun Chen ◽  
Nirzari Gupta ◽  
...  
Keyword(s):  
Nucleic Acids ◽  
Defense Mechanisms ◽  
The Body ◽  
Stimuli Responsive ◽  
Triggered Release ◽  
Quadruplex Dna ◽  
Nucleic Acid Therapeutics ◽  
Wide Range ◽  
G Quadruplex ◽  
Hydrogel Capsules

Nucleic acid therapeutics have the potential to be the most effective disease treatment strategy due to their intrinsic precision and selectivity for coding highly specific biological processes. However, freely administered nucleic acids of any type are quickly destroyed or rendered inert by a host of defense mechanisms in the body. In this work, we address the challenge of using nucleic acids as drugs by preparing stimuli responsive poly(methacrylic acid)/poly(N-vinylpyrrolidone) (PMAA/PVPON)n multilayer hydrogel capsules loaded with ~7 kDa G-quadruplex DNA. The capsules are shown to release their DNA cargo on demand in response to both enzymatic and ultrasound (US)-triggered degradation. The unique structure adopted by the G-quadruplex is essential to its biological function and we show that the controlled release from the microcapsules preserves the basket conformation of the oligonucleotide used in our studies. We also show that the (PMAA/PVPON) multilayer hydrogel capsules can encapsulate and release ~450 kDa double stranded DNA. The encapsulation and release approaches for both oligonucleotides in multilayer hydrogel microcapsules developed here can be applied to create methodologies for new therapeutic strategies involving the controlled delivery of sensitive biomolecules. Our study provides a promising methodology for the design of effective carriers for DNA vaccines and medicines for a wide range of immunotherapies, cancer therapy and/or tissue regeneration therapies in the future.

Targeting DNA G-Quadruplex Structures with Peptide Nucleic Acids

2012 ◽  
Vol 18 (14) ◽  
pp. 1984-1991 ◽  
Author(s):  
Igor G. Panyutin ◽  
Mykola I. Onyshchenko ◽  
Ethan A. Englund ◽  
Daniel H. Appella ◽  
Ronald D. Neumann
Keyword(s):  
Nucleic Acids ◽  
Peptide Nucleic Acids ◽  
G Quadruplex

Hybridization of G-Quadruplex-Forming Peptide Nucleic Acids to Guanine-Rich DNA Templates Inhibits DNA Polymerase η Extension

Biochemistry ◽  
2014 ◽  
Vol 53 (32) ◽  
pp. 5315-5322 ◽  
Author(s):  
Connor T. Murphy ◽  
Anisha Gupta ◽  
Bruce A. Armitage ◽  
Patricia L. Opresko
Keyword(s):  
Nucleic Acids ◽  
Dna Polymerase ◽  
Peptide Nucleic Acids ◽  
Dna Templates ◽  
G Quadruplex

scholarly journals Reactive OFF-ON type alkylating agents for higher-ordered structures of nucleic acids

2019 ◽  
Vol 47 (13) ◽  
pp. 6578-6589 ◽  
Author(s):  
Kazumitsu Onizuka ◽  
Madoka E Hazemi ◽  
Norihiro Sato ◽  
Gen-ichiro Tsuji ◽  
Shunya Ishikawa ◽  
...  
Keyword(s):  
Nucleic Acids ◽  
Alkylating Agents ◽  
Side Reactions ◽  
Ordered Structures ◽  
Dna And Rna ◽  
G Quadruplex ◽  
Significant Research ◽  
Order Structures ◽  
Ap Site ◽  
Double Strand Dna

Abstract Higher-ordered structure motifs of nucleic acids, such as the G-quadruplex (G-4), mismatched and bulge structures, are significant research targets because these structures are involved in genetic control and diseases. Selective alkylation of these higher-order structures is challenging due to the chemical instability of the alkylating agent and side-reactions with the single- or double-strand DNA and RNA. We now report the reactive OFF-ON type alkylating agents, vinyl-quinazolinone (VQ) precursors with a sulfoxide, thiophenyl or thiomethyl group for the OFF-ON control of the vinyl reactivity. The stable VQ precursors conjugated with aminoacridine, which bind to the G-4 DNA, selectively reacted with a T base on the G-4 DNA in contrast to the single- and double-strand DNA. Additionally, the VQ precursor reacted with the T or U base in the AP-site, G-4 RNA and T-T mismatch structures. These VQ precursors would be a new candidate for the T or U specific alkylation in the higher-ordered structures of nucleic acids.

scholarly journals Guanine base stacking in G-quadruplex nucleic acids

2012 ◽  
Vol 41 (3) ◽  
pp. 2034-2046 ◽  
Author(s):  
Christopher Jacques Lech ◽  
Brahim Heddi ◽  
Anh Tuân Phan
Keyword(s):  
Nucleic Acids ◽  
Base Stacking ◽  
G Quadruplex ◽  
Guanine Base

Targeting unimolecular G-quadruplex nucleic acids: a new paradigm for the drug discovery?

2014 ◽  
Vol 9 (10) ◽  
pp. 1167-1187 ◽  
Author(s):  
Lucia Parrotta ◽  
Francesco Ortuso ◽  
Federica Moraca ◽  
Roberta Rocca ◽  
Giosuè Costa ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Nucleic Acids ◽  
New Paradigm ◽  
G Quadruplex

Targeting G-quadruplex nucleic acids with heterocyclic alkaloids and their derivatives

2015 ◽  
Vol 97 ◽  
pp. 538-551 ◽  
Author(s):  
Yun-Xia Xiong ◽  
Zhi-Shu Huang ◽  
Jia-Heng Tan
Keyword(s):  
Nucleic Acids ◽  
G Quadruplex
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