title: Nylon-3 polymers with selective antifungal activity.
abstract: Host-defense peptides inhibit bacterial growth but show little toxicity toward mammalian cells. A variety of synthetic polymers have been reported to mimic this antibacterial selectivity; however, achieving comparable selectivity for fungi is more difficult because these pathogens are eukaryotes. Here we report nylon-3 polymers based on a novel subunit that display potent antifungal activity (MIC = 3.1 μg/mL for Candida albicans ) and favorable selectivity (IC10 > 400 μg/mL for 3T3 fibroblast toxicity; HC10 > 400 μg/mL for hemolysis).
authors.affiliation: Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706, USA.
authors.forename: Runhui
authors.initials: R
authors.lastname: Liu
authors.forename: Xinyu
authors.initials: X
authors.lastname: Chen
authors.forename: Zvi
authors.initials: Z
authors.lastname: Hayouka
authors.forename: Saswata
authors.initials: S
authors.lastname: Chakraborty
authors.forename: Shaun P
authors.initials: SP
authors.lastname: Falk
authors.forename: Bernard
authors.initials: B
authors.lastname: Weisblum
authors.forename: Kristyn S
authors.initials: KS
authors.lastname: Masters
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Gellman
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D002176:Candida albicans / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects*; D006461:Hemolysis; D051379:Mice; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D009757:Nylons / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D009757:Nylons
references.citation: Biochemistry. 1996 Sep 24;35(38):12612-22
references.pmid: 8823199
references.citation: J Am Chem Soc. 2002 Oct 30;124(43):12774-85
references.pmid: 12392424
references.citation: Biochemistry. 2004 Jun 1;43(21):6393-403
references.pmid: 15157073
references.citation: Sci Transl Med. 2012 Dec 19;4(165):165rv13
references.pmid: 23253612
references.citation: Chembiochem. 2010 Jul 5;11(10):1356-60
references.pmid: 20503219
references.citation: J Mol Biol. 2008 May 23;379(1):38-50
references.pmid: 18440552
references.citation: Proc Natl Acad Sci U S A. 2001 May 22;98(11):5981-5
references.pmid: 11353851
references.citation: J Am Chem Soc. 2004 Jun 9;126(22):6848-9
references.pmid: 15174837
references.citation: Macromol Biosci. 2011 Nov 10;11(11):1499-504
references.pmid: 21818858
references.citation: J Am Chem Soc. 2009 Feb 4;131(4):1589-97
references.pmid: 19125651
references.citation: Curr Pharm Des. 2002;8(9):727-42
references.pmid: 11945168
references.citation: J Am Chem Soc. 2003 Oct 8;125(40):12092-3
references.pmid: 14518985
references.citation: J Am Chem Soc. 2009 Jul 22;131(28):9735-45
references.pmid: 19601684
references.citation: Proc Natl Acad Sci U S A. 1990 Jun;87(12):4761-5
references.pmid: 1693777
references.citation: Biopolymers. 1995;37(2):105-22
references.pmid: 7893944
references.citation: Curr Pharm Des. 2009;15(21):2377-92
references.pmid: 19601838
references.citation: Antimicrob Agents Chemother. 2006 Jul;50(7):2384-94
references.pmid: 16801416
references.citation: J Am Chem Soc. 2005 Mar 30;127(12):4128-9
references.pmid: 15783168
references.citation: J Am Chem Soc. 2006 Oct 4;128(39):12630-1
references.pmid: 17002340
references.citation: Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):2794-9
references.pmid: 18287037
references.citation: ACS Chem Biol. 2009 Jul 17;4(7):567-79
references.pmid: 19518070
references.citation: J Intern Med. 2003 Sep;254(3):197-215
references.pmid: 12930229
references.citation: Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):6968-73
references.pmid: 19359494
references.citation: Antimicrob Agents Chemother. 2011 Jan;55(1):417-20
references.pmid: 20956607
references.citation: Curr Med Res Opin. 2009 Dec;25(12):3011-20
references.pmid: 19849324
references.citation: Biopolymers. 2000;55(1):4-30
references.pmid: 10931439
references.citation: Angew Chem Int Ed Engl. 2004 Feb 20;43(9):1158-62
references.pmid: 14983462
references.citation: Int J Mol Sci. 2009 Sep 09;10(9):3951-3970
references.pmid: 19865528
references.citation: Proc Natl Acad Sci U S A. 2006 Oct 24;103(43):15997-6002
references.pmid: 17038500
references.citation: Angew Chem Int Ed Engl. 2006 Oct 13;45(40):6759-62
references.pmid: 16969889
references.citation: Rev Iberoam Micol. 2009 Dec 31;26(4):223-7
references.pmid: 19836985
references.citation: J Am Chem Soc. 2006 May 3;128(17):5776-85
references.pmid: 16637646
references.citation: Appl Microbiol Biotechnol. 2011 Feb;89(3):475-92
references.pmid: 20953604
references.citation: Nat Mater. 2011 Feb;10(2):149-56
references.pmid: 21151166
references.citation: Org Lett. 2004 Feb 19;6(4):557-60
references.pmid: 14961622
references.citation: Eur J Biochem. 2002 Aug;269(16):3869-80
references.pmid: 12180963
references.citation: Antimicrob Agents Chemother. 2012 Nov;56(11):5603-11
references.pmid: 22908154
references.citation: J Am Chem Soc. 2012 Oct 3;134(39):16255-64
references.pmid: 22937875
references.citation: Biomacromolecules. 2010 May 10;11(5):1286-90
references.pmid: 20380430
references.citation: Biomacromolecules. 2007 Jan;8(1):19-23
references.pmid: 17206783
references.citation: J Am Chem Soc. 2002 Jun 26;124(25):7324-30
references.pmid: 12071741
references.citation: Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5110-4
references.pmid: 11959961
references.citation: Biol Chem. 2001 Apr;382(4):597-619
references.pmid: 11405223
references.citation: Acc Chem Res. 2010 Jan 19;43(1):30-9
references.pmid: 19813703
references.citation: J Am Chem Soc. 2009 Nov 25;131(46):16779-89
references.pmid: 19886604
references.citation: Biochim Biophys Acta. 1999 Dec 15;1462(1-2):55-70
references.pmid: 10590302
references.citation: Biomacromolecules. 2012 Apr 9;13(4):1100-5
references.pmid: 22455338
references.citation: J Am Chem Soc. 2001 Aug 8;123(31):7553-9
references.pmid: 11480975
references.citation: Cell Mol Life Sci. 2011 Jul;68(13):2161-76
references.pmid: 21573784
references.citation: Nat Chem. 2011 May;3(5):409-14
references.pmid: 21505501
references.citation: Science. 1972 Jul 28;177(4046):314-22
references.pmid: 4113805
references.citation: Angew Chem Int Ed Engl. 2008;47(7):1250-4
references.pmid: 18181131
references.citation: Antimicrob Agents Chemother. 2010 Oct;54(10):4049-58
references.pmid: 20696877
references.citation: J Am Chem Soc. 2007 Dec 19;129(50):15474-6
references.pmid: 18034491
references.citation: Clin Infect Dis. 2004 Aug 1;39(3):309-17
references.pmid: 15306996
references.citation: Nat Biotechnol. 2006 Dec;24(12):1551-7
references.pmid: 17160061
references.citation: Pharmacol Rev. 2003 Mar;55(1):27-55
references.pmid: 12615953
references.citation: J Am Chem Soc. 2004 Dec 8;126(48):15870-5
references.pmid: 15571411
references.citation: Philos Trans R Soc Lond B Biol Sci. 1980 May 16;289(1036):191-5
references.pmid: 6109315
references.citation: Org Lett. 2007 Apr 12;9(8):1549-52
references.pmid: 17352488
references.citation: J Am Chem Soc. 2007 Dec 19;129(50):15615-22
references.pmid: 18041836
references.citation: Nature. 2000 Apr 6;404(6778):565
references.pmid: 10766230
references.citation: Nature. 2002 Jan 24;415(6870):389-95
references.pmid: 11807545
references.citation: Biomacromolecules. 2009 Nov 9;10(11):3098-107
references.pmid: 19803480
references.citation: J Am Chem Soc. 2008 Jul 30;130(30):9836-43
references.pmid: 18593128
references.citation: FEBS Lett. 1999 Apr 23;449(2-3):105-10
references.pmid: 10338113
references.citation: Biomacromolecules. 2011 Nov 14;12(11):3839-43
references.pmid: 21955251