Multivalency in the recognition and antagonism of a HIV TAR RNA-TAT assembly using an aminoglycoside benzimidazole scaffold

Organic & Biomolecular Chemistry
Sunil KumarDev P Arya

Abstract

Recognition of RNA by high-affinity binding small molecules is crucial for expanding existing approaches in RNA recognition, and for the development of novel RNA binding drugs. A novel neomycin dimer benzimidazole conjugate 5 (DPA 83) was synthesized by conjugating a neomycin-dimer with a benzimidazole alkyne using click chemistry to target multiple binding sites on HIV TAR RNA. Ligand 5 significantly enhances the thermal stability of HIV TAR RNA and interacts stoichiometrically with HIV TAR RNA with a low nanomolar affinity. 5 displayed enhanced binding compared to its individual building blocks including the neomycin dimer azide and benzimidazole alkyne. In essence, a high affinity multivalent ligand was designed and synthesized to target HIV TAR RNA.

References

Apr 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·J Tao, A D Frankel
Jan 1, 1994·Annual Review of Biochemistry·K A Jones, B M Peterlin
May 18, 1999·Archives of Biochemistry and Biophysics·T M Rana, K T Jeang
Nov 11, 1999·Proceedings of the National Academy of Sciences of the United States of America·S HwangT M Rana
Sep 15, 2000·Bioorganic & Medicinal Chemistry Letters·D P Arya, R L Coffee
Jun 8, 2001·Journal of the American Chemical Society·D P AryaA I Abramovitch
Jun 21, 2001·Journal of the American Chemical Society·D L BogerM P Hedrick
Nov 1, 2001·Journal of the American Chemical Society·D P AryaI Charles
Jul 18, 2002·Chemical Communications : Chem Comm·Liang XueDev P Arya
Mar 27, 2003·Journal of the American Chemical Society·Dev P AryaLiang Xue
Aug 23, 2006·Biochemistry·Bert Willis, Dev P Arya
Jun 25, 2008·Bioorganic & Medicinal Chemistry Letters·Nicholas N ShawDev P Arya
Jul 9, 2009·Proceedings of the National Academy of Sciences of the United States of America·Amy DavidsonGabriele Varani
Dec 17, 2009·Biochemistry·Bert Willis, Dev P Arya
Oct 5, 2010·Biochemistry·Nihar RanjanDev P Arya
Nov 16, 2010·Accounts of Chemical Research·Dev P Arya
Jul 16, 2011·Bioorganic & Medicinal Chemistry Letters·Sunil Kumar, Dev P Arya
Aug 26, 2011·Biochemistry·Hongjuan XiDev P Arya
Feb 22, 2012·Biochemistry·Sunil KumarDev P Arya
May 24, 2013·Chemical Communications : Chem Comm·Nihar RanjanDev P Arya
Sep 10, 2013·Bioorganic & Medicinal Chemistry Letters·Nihar RanjanDev P Arya
Nov 21, 2013·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Nihar Ranjan, Dev P Arya
Mar 19, 2014·Bioorganic & Medicinal Chemistry·Bert Willis, Dev P Arya
Oct 1, 2015·Chemical Science·Smita NaharSouvik Maiti

❮ Previous
Next ❯

Citations

Oct 25, 2016·ACS Chemical Biology·Brian P CharretteThomas Hermann
Dec 23, 2016·Journal of the American Chemical Society·Christopher S EubanksAmanda E Hargrove
Dec 21, 2016·Organic & Biomolecular Chemistry·Ananya PaulW David Wilson
Nov 12, 2016·Dalton Transactions : an International Journal of Inorganic Chemistry·Rubén Gil-GarcíaJavier García-Tojal
Apr 25, 2020·Angewandte Chemie·Rakesh PaulJyotirmayee Dash
Jun 17, 2016·Wiley Interdisciplinary Reviews. RNA·Thomas Hermann
Sep 23, 2020·Archiv der Pharmazie·Lian-Shun FengDuan Liu
Jan 1, 2018·Supramolecular Chemistry·M D ArifuzzamanYan Zhao
Aug 12, 2017·MedChemComm·Neeraj N PatwardhanAmanda E Hargrove
Jun 17, 2020·Chemistry : a European Journal·Klara AradiMaria Duca
Feb 27, 2020·Antibiotics·Lanqing YingKurt Fredrick
Nov 18, 2020·Chemical Communications : Chem Comm·Amanda E Hargrove
Dec 19, 2020·The Journal of Biological Chemistry·Aline Umuhire Juru, Amanda E Hargrove
Jun 25, 2021·Chemical Reviews·Anand K AgrahariVinod K Tiwari

❮ Previous
Next ❯

Related Concepts

Related Feeds

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Anthelmintics

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.

© 2022 Meta ULC. All rights reserved