Synthetic Mimic of Antimicrobial Peptide with Nonmembrane-disrupting Antibacterial Properties

Overview

Journal Biomacromolecules

Publisher American Chemical Society

Specialties Biochemistry
Biology
Molecular Biology

Date 2008 Oct 15

PMID 18850741

Citations 51

Authors

Gregory J Gabriel

Ahmad E Madkour

Jeffrey M Dabkowski

Christopher F Nelson

Klaus Nusslein

Gregory N Tew

Affiliations

Soon will be listed here.

Abstract

Polyguanidinium oxanorbornene ( PGON) was synthesized from norbornene monomers via ring-opening metathesis polymerization. This polymer was observed to be strongly antibacterial against Gram-negative and Gram-positive bacteria as well as nonhemolytic against human red blood cells. Time-kill studies indicated that this polymer is lethal and not just bacteriostatic. In sharp contrast to previously reported SMAMPs (synthetic mimics of antimicrobial peptides), PGON did not disrupt membranes in vesicle-dye leakage assays and microscopy experiments. The unique biological properties of PGON, in same ways similar to cell-penetrating peptides, strongly encourage the examination of other novel guanidino containing macromolecules as powerful and selective antimicrobial agents.

Citing Articles

Cholic-Acid Derived, Guanidine-Functionalized Polymers as Broad-Spectrum Antimicrobial Agents.

Xiong Y, Nayanathara U, Lai X, Huang X, Zhang C, Yuen D ACS Omega. 2024; 9(49):48738-48747.

PMID: 39676976 PMC: 11635482. DOI: 10.1021/acsomega.4c08266.

Salt-Responsive Switchable Block Copolymer Brushes with Antibacterial and Antifouling Properties.

Methling R, Greiter M, Al-Zawity J, Muller M, Schonherr H, Kuckling D Macromol Biosci. 2024; 25(1):e2400261.

PMID: 39601460 PMC: 11727821. DOI: 10.1002/mabi.202400261.

Effects of Secondary Amine and Molecular Weight on the Biological Activities of Cationic Amphipathic Antimicrobial Macromolecules.

Shao Z, Luo H, Nguyen T, Wong E Biomacromolecules. 2024; 25(10):6899-6912.

PMID: 39312184 PMC: 11483101. DOI: 10.1021/acs.biomac.4c01137.

Ring-opening metathesis polymerization of -methylpyridinium-fused norbornenes to access antibacterial main-chain cationic polymers.

Hancock S, Yuntawattana N, Diep E, Maity A, Tran A, Schiffman J Proc Natl Acad Sci U S A. 2023; 120(51):e2311396120.

PMID: 38079554 PMC: 10742381. DOI: 10.1073/pnas.2311396120.

Structure-Activity Relationships of the Antimicrobial Peptide Natural Product Apidaecin.

Skowron K, Baliga C, Johnson T, Kremiller K, Castroverde A, Dean T J Med Chem. 2023; 66(17):11831-11842.

PMID: 37603874 PMC: 10768847. DOI: 10.1021/acs.jmedchem.3c00406.

References

Patch J, Barron A . Helical peptoid mimics of magainin-2 amide. J Am Chem Soc. 2003; 125(40):12092-3. DOI: 10.1021/ja037320d. View

Fillon Y, Anderson J, Chmielewski J . Cell penetrating agents based on a polyproline helix scaffold. J Am Chem Soc. 2005; 127(33):11798-803. DOI: 10.1021/ja052377g. View

Kolonko E, Kiessling L . A polymeric domain that promotes cellular internalization. J Am Chem Soc. 2008; 130(17):5626-7. PMC: 3216674. DOI: 10.1021/ja8001716. View

Kuroda K, DeGrado W . Amphiphilic polymethacrylate derivatives as antimicrobial agents. J Am Chem Soc. 2005; 127(12):4128-9. DOI: 10.1021/ja044205+. View

Gabriel G, Som A, Madkour A, Eren T, Tew G . Infectious Disease: Connecting Innate Immunity to Biocidal Polymers. Mater Sci Eng R Rep. 2007; 57(1-6):28-64. PMC: 2153456. DOI: 10.1016/j.mser.2007.03.002. View

Pantos A, Tsogas I, Paleos C . Guanidinium group: a versatile moiety inducing transport and multicompartmentalization in complementary membranes. Biochim Biophys Acta. 2008; 1778(4):811-23. DOI: 10.1016/j.bbamem.2007.12.003. View

Ge Y, MACDONALD D, Holroyd K, Thornsberry C, Wexler H, Zasloff M . In vitro antibacterial properties of pexiganan, an analog of magainin. Antimicrob Agents Chemother. 1999; 43(4):782-8. PMC: 89207. DOI: 10.1128/AAC.43.4.782. View

Miyatake T, Nishihara M, Matile S . A cost-effective method for the optical transduction of chemical reactions. Application to hyaluronidase inhibitor screening with polyarginine-counteranion complexes in lipid bilayers. J Am Chem Soc. 2006; 128(38):12420-1. DOI: 10.1021/ja064732o. View

Rothbard J, Kreider E, Vandeusen C, Wright L, Wylie B, Wender P . Arginine-rich molecular transporters for drug delivery: role of backbone spacing in cellular uptake. J Med Chem. 2002; 45(17):3612-8. DOI: 10.1021/jm0105676. View

10.

Deglane G, Abes S, Michel T, Prevot P, Vives E, Debart F . Impact of the guanidinium group on hybridization and cellular uptake of cationic oligonucleotides. Chembiochem. 2006; 7(4):684-92. DOI: 10.1002/cbic.200500433. View

11.

Funhoff A, van Nostrum C, Lok M, Fretz M, Crommelin D, Hennink W . Poly(3-guanidinopropyl methacrylate): a novel cationic polymer for gene delivery. Bioconjug Chem. 2004; 15(6):1212-20. DOI: 10.1021/bc049864q. View

12.

Radzishevsky I, Rotem S, Bourdetsky D, Navon-Venezia S, Carmeli Y, Mor A . Improved antimicrobial peptides based on acyl-lysine oligomers. Nat Biotechnol. 2007; 25(6):657-9. DOI: 10.1038/nbt1309. View

13.

Ilker M, Nusslein K, Tew G, Coughlin E . Tuning the hemolytic and antibacterial activities of amphiphilic polynorbornene derivatives. J Am Chem Soc. 2004; 126(48):15870-5. DOI: 10.1021/ja045664d. View

14.

Porter E, Wang X, Lee H, Weisblum B, Gellman S . Non-haemolytic beta-amino-acid oligomers. Nature. 2000; 404(6778):565. DOI: 10.1038/35007145. View

15.

Schmitt M, Weisblum B, Gellman S . Interplay among folding, sequence, and lipophilicity in the antibacterial and hemolytic activities of alpha/beta-peptides. J Am Chem Soc. 2007; 129(2):417-28. DOI: 10.1021/ja0666553. View

16.

Schroder T, Niemeier N, Afonin S, Ulrich A, Krug H, Brase S . Peptoidic amino- and guanidinium-carrier systems: targeted drug delivery into the cell cytosol or the nucleus. J Med Chem. 2008; 51(3):376-9. DOI: 10.1021/jm070603m. View

17.

Futaki S, Suzuki T, Ohashi W, Yagami T, Tanaka S, Ueda K . Arginine-rich peptides. An abundant source of membrane-permeable peptides having potential as carriers for intracellular protein delivery. J Biol Chem. 2000; 276(8):5836-40. DOI: 10.1074/jbc.M007540200. View

18.

Som A, Tew G . Influence of lipid composition on membrane activity of antimicrobial phenylene ethynylene oligomers. J Phys Chem B. 2008; 112(11):3495-502. PMC: 3774278. DOI: 10.1021/jp077487j. View

19.

Troeira Henriques S, Melo M, Castanho M . Cell-penetrating peptides and antimicrobial peptides: how different are they?. Biochem J. 2006; 399(1):1-7. PMC: 1570158. DOI: 10.1042/BJ20061100. View

20.

Mitchell D, Kim D, Steinman L, Fathman C, Rothbard J . Polyarginine enters cells more efficiently than other polycationic homopolymers. J Pept Res. 2000; 56(5):318-25. DOI: 10.1034/j.1399-3011.2000.00723.x. View