Isosteric substitution in cationic-amphiphilic polymers reveals an important role for hydrogen bonding in bacterial membrane interactions

Chemical Science
Divakara S S M UppuJayanta Haldar

Abstract

Biomimetic antibacterial polymers, the functional mimics of antimicrobial peptides (AMPs), targeting the bacterial cell membrane have been developed to combat the problem of antibiotic resistance. Amphiphilicity, a balance of cationic charge and hydrophobicity, in these polymers has been shown to be pivotal for their selective interactions with anionic lipid membranes of bacteria instead of zwitterionic mammalian (human erythrocyte) membranes. However, it is unclear if and to what extent hydrogen bonding in amphiphilic antibacterial polymers contributes to this membrane binding specificity. To address this, we employ isosteric substitution of ester with amide moieties that differ in their potency for hydrogen bonding in the side chains of N-alkyl maleimide based amphiphilic polymers. Our studies reveal that amide polymer (AC3P) is a potent antibacterial agent with high membrane-disrupting properties compared to its ester counterpart (EC3P). To understand these differences we performed bio-physical experiments and molecular dynamics (MD) simulations which showed strong interactions of AC3P including hydrogen bonding with lipid head groups of bacterial model lipid bilayers, that are absent in EC3P, make them selective for bacteri...Continue Reading

References

Mar 14, 1997·Biochimica Et Biophysica Acta·J Seelig
Apr 15, 2000·Nature·E A PorterS H Gellman
Jan 25, 2002·Nature·Michael Zasloff
Mar 5, 2003·Pharmacological Reviews·Michael R Yeaman, Nannette Y Yount
Oct 2, 2003·Journal of the American Chemical Society·James A Patch, Annelise E Barron
Feb 26, 2004·Angewandte Chemie·Dahui LiuWilliam F DeGrado
Feb 11, 2005·Nature Reviews. Microbiology·Kim A Brogden
Jun 17, 2005·Organic Letters·Cara L JenkinsRonald T Raines
Oct 14, 2005·Journal of Computational Chemistry·James C PhillipsKlaus Schulten
Dec 13, 2006·Nature Biotechnology·Robert E W Hancock, Hans-Georg Sahl
May 29, 2007·Nature Biotechnology·Inna S RadzishevskyAmram Mor
Jul 19, 2008·Science·Gary Taubes
Jan 29, 2009·Biochemistry·Gabriela KlocekJoachim Seelig
May 26, 2010·The Journal of Physical Chemistry. B·Jeffery B KlaudaRichard W Pastor
Jun 23, 2010·Proceedings of the National Academy of Sciences of the United States of America·Henrik Strahl, Leendert W Hamoen
Apr 21, 2011·Nature Chemistry·Fredrik NederbergYi-Yan Yang
Apr 6, 2012·Journal of Medicinal Chemistry·Youhong NiuJianfeng Cai
Nov 14, 2012·Journal of Chemical Information and Modeling·K VanommeslaegheA D MacKerell
Nov 14, 2012·Journal of Chemical Information and Modeling·K Vanommeslaeghe, A D MacKerell
Feb 7, 2013·The Journal of Physical Chemistry. B·Vedagopuram Sreekanth, Avinash Bajaj
Jul 9, 2013·Macromolecular Bioscience·Haruko TakahashiKenichi Kuroda
Jul 23, 2013·Chemical Communications : Chem Comm·Divakara S S M UppuJayanta Haldar
Jul 28, 2013·Nature·Maryn McKenna
Sep 7, 2013·Accounts of Chemical Research·Federica SgolastraGregory N Tew
Mar 8, 2014·Journal of the American Chemical Society·Runhui LiuSamuel H Gellman
Apr 8, 2014·Proceedings of the National Academy of Sciences of the United States of America·Michaela WenzelJulia Elisabeth Bandow
Apr 30, 1998·The Journal of Physical Chemistry. B·A D MacKerellM Karplus
Sep 1, 2014·The Journal of Chemical Physics·Upayan BaulSatyavani Vemparala
Oct 16, 2015·Proceedings of the National Academy of Sciences of the United States of America·Menghua XiongJianjun Cheng
Feb 4, 2016·Biomacromolecules·Divakara S S M Uppu, Jayanta Haldar

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Citations

Nov 9, 2018·World Journal of Microbiology & Biotechnology·Tapas DasUtpal Ch De
Mar 21, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Saptarshi ChakrabortySuhrit Ghosh
Apr 28, 2018·Chemical Communications : Chem Comm·Mohini M KonaiJayanta Haldar
Sep 22, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Yueming WuRunhui Liu
Oct 9, 2020·International Journal of Molecular Sciences·Joanna Izabela LachowiczMariusz Jaremko
Jun 5, 2021·Langmuir : the ACS Journal of Surfaces and Colloids·Akshi Deshwal, Subhabrata Maiti
Oct 9, 2017·ACS Biomaterials Science & Engineering·Steven MankociAbraham Joy
Jan 20, 2021·ACS Biomaterials Science & Engineering·Ranajit BarmanSuhrit Ghosh
Dec 9, 2021·ACS Infectious Diseases·Yash AcharyaJayanta Haldar
Jan 20, 2022·Chemical Communications : Chem Comm·Yash AcharyaJayanta Haldar

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Methods Mentioned

BETA
isothermal titration calorimetry
Assay
isothermal titration calorimeter

Software Mentioned

CHARMM
Origin
NAMD
CGenFF

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