Engineering of anti-cancer g-quadruplex nucleic acids and anti-bacterial protein fibers

A facile imide coupling strategy for the one-step preparation of G‑quadruplex ligands with varied core chemistries is described. The G‑quadruplex stabilization, anticancer and antiparasitic activity of a library of nine compounds was examined, identifying a nanomolar inhibitor of T. brucei with 78‑fold selectivity over MRC5 cells, and strong stabilization of G‑quadruplex nucleic acids.

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Imide Condensation as a Strategy for the Synthesis of Core Diversified G-Quadruplex Ligands with Anti-Cancer and Anti-Parasitic Activity

10.26434/chemrxiv.11955870 ◽

2021 ◽

Author(s):

Steven T. G. Street ◽

pablo Peñalver ◽

Michael O'Hagan ◽

Gregory J. Hollingworth ◽

Juan Carlos Morales ◽

...

Keyword(s):

Nucleic Acids ◽

Antiparasitic Activity ◽

Strong Stabilization ◽

Anti Cancer ◽

G Quadruplex ◽

Coupling Strategy ◽

One Step ◽

Parasitic Activity ◽

The One

A facile imide coupling strategy for the one-step preparation of G‑quadruplex ligands with varied core chemistries is described. The G‑quadruplex stabilization, anticancer and antiparasitic activity of a library of nine compounds was examined, identifying a nanomolar inhibitor of T. brucei with 78‑fold selectivity over MRC5 cells, and strong stabilization of G‑quadruplex nucleic acids.

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Imide Condensation as a Strategy for the Synthesis of Core Diversified G-Quadruplex Ligands with Anti-Cancer and Anti-Parasitic Activity

10.26434/chemrxiv.11955870.v1 ◽

2020 ◽

Author(s):

Steven T. G. Street ◽

pablo Peñalver ◽

Michael O'Hagan ◽

Gregory J. Hollingworth ◽

Juan Carlos Morales ◽

...

Keyword(s):

Nucleic Acids ◽

Antiparasitic Activity ◽

Strong Stabilization ◽

Anti Cancer ◽

G Quadruplex ◽

Coupling Strategy ◽

One Step ◽

Parasitic Activity ◽

The One

A facile imide coupling strategy for the one-step preparation of G‑quadruplex ligands with varied core chemistries is described. The G‑quadruplex stabilization, anticancer and antiparasitic activity of a library of nine compounds was examined, identifying a nanomolar inhibitor of T. brucei with 78‑fold selectivity over MRC5 cells, and strong stabilization of G‑quadruplex nucleic acids.

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

Polymers ◽

10.3390/polym10121342 ◽

2018 ◽

Vol 10 (12) ◽

pp. 1342 ◽

Cited By ~ 4

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.

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