The inhibitory properties of acidic functionalised calix[4]arenes on human papillomavirus pentamer formation

© 2020 Informa UK Limited, trading as Taylor & Francis Group. Human Papillomavirus (HPV) is the leading cause of cervical cancer, with only some HPV types prevented with vaccines and no treatments for the viral infection itself. One way to target viral infection is by inhibiting the assemb...

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Main Authors: Goh, Ching Yong, Fu, D.Y., Duncan, Caitlin, Tinker, Adam, Li, F., Mocerino, Mauro, Ogden, Mark, Wu, Y.
Format: Journal Article
Language:English
Published: TAYLOR & FRANCIS LTD 2020
Subjects:
Online Access:http://hdl.handle.net/20.500.11937/80239
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author Goh, Ching Yong
Fu, D.Y.
Duncan, Caitlin
Tinker, Adam
Li, F.
Mocerino, Mauro
Ogden, Mark
Wu, Y.
author_facet Goh, Ching Yong
Fu, D.Y.
Duncan, Caitlin
Tinker, Adam
Li, F.
Mocerino, Mauro
Ogden, Mark
Wu, Y.
author_sort Goh, Ching Yong
building Curtin Institutional Repository
collection Online Access
description © 2020 Informa UK Limited, trading as Taylor & Francis Group. Human Papillomavirus (HPV) is the leading cause of cervical cancer, with only some HPV types prevented with vaccines and no treatments for the viral infection itself. One way to target viral infection is by inhibiting the assembly of the L1 monomer into a pentamer, which forms the viral capsid. Four calix[4]arene compounds functionalised with D- and L-aspartic and glutamic acid and an iminodiacetic functionalised calix[4]arene were synthesised and tested for L1 pentamer formation inhibition. The amino acid functionalised calix[4]arene derivatives showed millimolar inhibition (IC50 = 0.72 to 2.67 mM) of pentamer formation, with little difference between the stereoisomers. The iminodiacetic acid calix[4]arene derivative showed no inhibitory properties, despite sharing structural similarities with the four other calix[4]arenes. Confirmation of binding the negatively charged compounds to the positive residues of the L1 protein was achieved by trypsin digestion. This study is helpful in the development of cost-effective inhibitors to prevent HPV assembly.
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spelling curtin-20.500.11937-802392021-07-16T00:30:07Z The inhibitory properties of acidic functionalised calix[4]arenes on human papillomavirus pentamer formation Goh, Ching Yong Fu, D.Y. Duncan, Caitlin Tinker, Adam Li, F. Mocerino, Mauro Ogden, Mark Wu, Y. Science & Technology Physical Sciences Chemistry, Multidisciplinary Chemistry Calixarene human papillomavirus assembly inhibitor L1 pentamer amino acid CAPSID PROTEIN CALIXARENE AGENTS © 2020 Informa UK Limited, trading as Taylor & Francis Group. Human Papillomavirus (HPV) is the leading cause of cervical cancer, with only some HPV types prevented with vaccines and no treatments for the viral infection itself. One way to target viral infection is by inhibiting the assembly of the L1 monomer into a pentamer, which forms the viral capsid. Four calix[4]arene compounds functionalised with D- and L-aspartic and glutamic acid and an iminodiacetic functionalised calix[4]arene were synthesised and tested for L1 pentamer formation inhibition. The amino acid functionalised calix[4]arene derivatives showed millimolar inhibition (IC50 = 0.72 to 2.67 mM) of pentamer formation, with little difference between the stereoisomers. The iminodiacetic acid calix[4]arene derivative showed no inhibitory properties, despite sharing structural similarities with the four other calix[4]arenes. Confirmation of binding the negatively charged compounds to the positive residues of the L1 protein was achieved by trypsin digestion. This study is helpful in the development of cost-effective inhibitors to prevent HPV assembly. 2020 Journal Article http://hdl.handle.net/20.500.11937/80239 10.1080/10610278.2020.1779930 English TAYLOR & FRANCIS LTD fulltext
spellingShingle Science & Technology
Physical Sciences
Chemistry, Multidisciplinary
Chemistry
Calixarene
human papillomavirus
assembly inhibitor
L1 pentamer
amino acid
CAPSID PROTEIN
CALIXARENE
AGENTS
Goh, Ching Yong
Fu, D.Y.
Duncan, Caitlin
Tinker, Adam
Li, F.
Mocerino, Mauro
Ogden, Mark
Wu, Y.
The inhibitory properties of acidic functionalised calix[4]arenes on human papillomavirus pentamer formation
title The inhibitory properties of acidic functionalised calix[4]arenes on human papillomavirus pentamer formation
title_full The inhibitory properties of acidic functionalised calix[4]arenes on human papillomavirus pentamer formation
title_fullStr The inhibitory properties of acidic functionalised calix[4]arenes on human papillomavirus pentamer formation
title_full_unstemmed The inhibitory properties of acidic functionalised calix[4]arenes on human papillomavirus pentamer formation
title_short The inhibitory properties of acidic functionalised calix[4]arenes on human papillomavirus pentamer formation
title_sort inhibitory properties of acidic functionalised calix[4]arenes on human papillomavirus pentamer formation
topic Science & Technology
Physical Sciences
Chemistry, Multidisciplinary
Chemistry
Calixarene
human papillomavirus
assembly inhibitor
L1 pentamer
amino acid
CAPSID PROTEIN
CALIXARENE
AGENTS
url http://hdl.handle.net/20.500.11937/80239