Cell penetrating thiazole peptides inhibit c-MYC expression via site-specific targeting of c-MYC G-quadruplex

Nucleic Acids Research
Debasish DuttaJyotirmayee Dash

Abstract

The structural differences among different G-quadruplexes provide an opportunity for site-specific targeting of a particular G-quadruplex structure. However, majority of G-quadruplex ligands described thus far show little selectivity among different G-quadruplexes. In this work, we delineate the design and synthesis of a crescent-shaped thiazole peptide that preferentially stabilizes c-MYC quadruplex over other promoter G-quadruplexes and inhibits c-MYC oncogene expression. Biophysical analysis such as Förster resonance energy transfer (FRET) melting and fluorescence spectroscopy show that the thiazole peptide TH3 can selectively interact with the c-MYC G-quadruplex over other investigated G-quadruplexes and duplex DNA. NMR spectroscopy reveals that peptide TH3 binds to the terminal G-quartets and capping regions present in the 5'- and 3'-ends of c-MYC G-quadruplex with a 2:1 stoichiometry; whereas structurally related distamycin A is reported to interact with quadruplex structures via groove binding and end stacking modes with 4:1 stoichiometry. Importantly, qRT-PCR, western blot and dual luciferase reporter assay show that TH3 downregulates c-MYC expression by stabilizing the c-MYC G-quadruplex in cancer cells. Moreover, TH3 ...Continue Reading

References

Apr 4, 1998·Nucleic Acids Research·T SimonssonM Kubista
May 20, 1999·Natural Product Reports·R S RoyC T Walsh
Aug 27, 2002·Proceedings of the National Academy of Sciences of the United States of America·Adam Siddiqui-JainLaurence H Hurley
May 29, 2003·Nucleic Acids Research·Melanie J CoccoNancy Maizels
Jan 1, 1953·Cold Spring Harbor Symposia on Quantitative Biology·J D WATSON, F H CRICK
Jul 15, 2004·Journal of the American Chemical Society·Anh Tuân PhanDinshaw J Patel
Feb 11, 2005·Chemical Reviews·Mark C BagleyXin Xiong
Apr 20, 2006·Journal of the American Chemical Society·Thomas S DexheimerLaurence H Hurley
Jun 21, 2006·Biochemistry·Himesh FernandoShankar Balasubramanian
Oct 19, 2006·Journal of the American Chemical Society·Katja JantosShankar Balasubramanian
May 3, 2007·Methods : a Companion to Methods in Enzymology·Anne De CianJean-Louis Mergny
Aug 2, 2007·Accounts of Chemical Research·Bernard Meunier
Dec 7, 2007·Journal of the American Chemical Society·Luigi MartinoAntonio Randazzo
Jun 20, 2008·Angewandte Chemie·Masayuki TeraKazuo Nagasawa
Sep 24, 2008·Organic Letters·Pablo García-Reynaga, Michael S VanNieuwenhze
Apr 3, 2010·Journal of Medicinal Chemistry·Suzanne G RzuczekJoseph E Rice
Apr 17, 2010·Journal of the American Chemical Society·Sandro CosconatiAntonio Randazzo
Nov 30, 2010·Genes & Cancer·Tracy A Brooks, Laurence H Hurley
Apr 2, 2011·Nature Reviews. Drug Discovery·Shankar BalasubramanianStephen Neidle
Jul 27, 2011·Chemical Society Reviews·Gavin W Collie, Gary N Parkinson
Nov 15, 2011·Bioconjugate Chemistry·Akash K Jain, Santanu Bhattacharya
Mar 3, 2012·Current Pharmaceutical Design·Rupesh NanjundaW David Wilson
Oct 4, 2012·Nature Reviews. Genetics·Matthew L BochmanVirginia A Zakian
May 9, 2014·ACS Chemical Biology·Anette BrockmannThomas Brunner
Feb 23, 2017·Nature Reviews. Molecular Cell Biology·Robert Hänsel-HertschShankar Balasubramanian
Nov 23, 2017·Chemical Science·Manish DebnathJyotirmayee Dash
Dec 2, 2017·Nucleic Acids Research·Giacomo PadroniGlenn A Burley

❮ Previous
Next ❯

Citations

Jul 28, 2018·Chemistry : a European Journal·Sefan AsamitsuHiroshi Sugiyama
Nov 9, 2018·The Journal of Biological Chemistry·André S Bachmann, Dirk Geerts
Jan 3, 2019·Angewandte Chemie·Manish DebnathJyotirmayee Dash
Jan 27, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sefan AsamitsuHiroshi Sugiyama
Jan 27, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Zhi-Yin SunTian-Miao Ou
Feb 1, 2020·Expert Opinion on Therapeutic Targets·Daniel Massó-VallésLaura Soucek
Feb 19, 2020·Topics in Current Chemistry·Jinwei DuanMegan E Kizer
Feb 14, 2019·Nucleic Acids Research·Qianqian ZhaiDengguo Wei
Jun 18, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Francesca Tessaro, Leonardo Scapozza
Apr 16, 2020·International Journal of Molecular Sciences·Kwang-Im OhJoon-Hwa Lee
Dec 12, 2020·The Journal of Biological Chemistry·Dagim Shiferaw TadeleJorrit M Enserink
Feb 12, 2021·Organic & Biomolecular Chemistry·Kazumitsu OnizukaFumi Nagatsugi
Feb 11, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Loukiani Savva, Savvas N Georgiades
Dec 12, 2020·ChemistryOpen·Alice PomeislováVáclav Veverka
Jan 31, 2021·Nature Communications·Haruka TsutsumiHiroaki Suga
Feb 23, 2021·Frontiers in Oncology·Ruochen LiuHongjuan Cui
Jun 4, 2020·Biochimica Et Biophysica Acta. General Subjects·Pallabi Sengupta, Subhrangsu Chatterjee
Mar 24, 2021·Bioorganic & Medicinal Chemistry Letters·Jingfang Zhao, Qianqian Zhai
Aug 23, 2020·Biochimica Et Biophysica Acta. Reviews on Cancer·Wenmeng WangGuangchao Sui
Apr 9, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Annoor AwadasseidWen Zhang
Apr 15, 2021·Chemistry : a European Journal·Raj PaulJyotirmayee Dash
Jul 3, 2021·Cancers·Victoria Sanchez-MartinJose Antonio Garcia-Salcedo
Jul 26, 2021·Biochimica Et Biophysica Acta. Reviews on Cancer·Nirali PandyaAmit Kumar
Jul 11, 2021·Nucleic Acids Research·Hisae Tateishi-Karimata, Naoki Sugimoto
Dec 24, 2020·Journal of Medicinal Chemistry·Ritapa ChaudhuriSantanu Bhattacharya
Dec 12, 2018·Journal of Medicinal Chemistry·Snehasish JanaJyotirmayee Dash
Sep 12, 2021·Nature Reviews. Clinical Oncology·Renumathy DhanasekaranDean W Felsher
Nov 12, 2021·Analytical Chemistry·Matteo ScalabrinSara N Richter

❮ Previous
Next ❯

Methods Mentioned

BETA
NMR
PCR
FRET
Fluorescence
transfection
flow cytometry
FACS
fluorescence-activated cell sorter
chemical shift
Fluorescence microscopy

Software Mentioned

ImageJ
OriginPro
Cell
- Quest Pro

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.