研究领域

Bioorganic Chemistry Materials Chemistry Physical Chemistry Sensor Science Biomedical Engineering

Antibiotic-resistant bacteria have been a significant concern to medical practice, diminishing the number of available treatment options by antibiotics. There is a compelling need to establish new antimicrobials that are active against antibiotic-resistant bacteria without contributing to emergent resistance development. Our laboratory focuses on a new molecular design of antimicrobial synthetic polymers with alternative mode of antibacterial action for multiple applications including pharmaceutical agents, antimicrobial coatings on catheters and implants, and dental composite fillings. Antimicrobial peptide-mimetic polymers To create new antimicrobial materials effective to drug resistant bacteria, our laboratory has developed the molecular mimicry of naturally occurring antimicrobial peptides using synthetic methacrylate polymers. These polymers are designed to mimic the cationic functionality and amphiphilic nature of antimicrobial peptides to act as membrane-active antimicrobial agents. These antimicrobial polymers represent the hallmarks of antimicrobial peptide such as antimicrobial activity against a broad spectrum of bacteria including antibiotic-resistant strains, low propensity for resistance development in bacteria, and no adverse toxicity against host cells. Anti-biofilm Coatings Bacteria proficiently adhere to synthetic surfaces of medical devices or implants, and establish matrix-encased bacterial communities, known as biofilms. This biofilm formation is a concern because the biofilm matrix protects resident bacteria from host-defense mechanisms and antibiotic challenges, resulting in chronic and recurrent bacterial infections. To prevent the biofilm formation, our laboratory has developed versatile polymeric materials for bactericidal or anti-fouling coatings by utilizing a mussel protein mimetic adhesive group or a star-shaped polymer nano-architecture.

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Baul, U.; Kuroda, K. and Vemparala, S. "Interaction of multiple biomimetic antimicrobial polymers with model bacterial membranes." J. Chem. Phys., 2014, 141(8), 84902. DOI:10.1063/1.4893440. Thoma, L. M.; Boles, B. R. and Kuroda, K. "Cationic Methacrylate Polymers as Topical Antimicrobial Agents against Staphylococcus aureus Nasal Colonization." Biomacromolecules, 2014, 15(8), 2933. DOI:10.1021/bm500557d. Totani, M.; Ando, T.; Terada, K.; Terashima, T.; Kim, I. Y.; Ohtsuki, C.; Xi, C.; Kuroda, K. and Tanihara, M. "Utilization of star-shaped polymer architecture in the creation of high-density polymer brush coatings for the prevention of platelet and bacteria adhesion." Biomater. Sci., 2014, 2, 1172. DOI:10.1039/C4BM00034J. Tsukamoto, M.; Kuroda, K.; Ramamoorthy, A. and Yasuhara, K. "Modulation of raft domains in a lipid bilayer by boundary-active cur cumin." Chem. Comm., 2014, 50(26), 3427. DOI:10.1039/c3cc47738j. Takahashi, H.; Palermo, E. F.; Yasuhara, K.; Caputo, G. A. and Kuroda, K. "Molecular Design, Structures, and Activity of Antimicrobial Peptide-Mimetic Polymers." Macromol. Biosci., 2013, 13(10), 1285. DOI:10.1002/mabi.201300126. Palermo, E. F.; Vemparala, S. and Kuroda, K. "Chapter 19. Antimicrobial Polymers: Molecular Design as Synthetic Mimics of Host-Defense Peptides." Tailored Polymer Architectures for Pharmaceutical and Biomedical Applications. ACS Symposium Series, 2013, Vol. 1135, 319. Chapter DOI:10.1021/bk-2013-1135.ch019. Hu, K.; Schmidt, N. W.; Zhu, R.; Jiang, Y. J.; Lai, G. H.; Wei, G.; Palermo, E. F.; Kuroda, K.; Wong, G. C. L. and Yang, L. H. "A Critical Evaluation of Random Copolymer Mimesis of Homogeneous Antimicrobial Peptides." Macromol., 2013, 46(5), 1908-1915. DOI:10.1021/ma302577e. Kuroda, K. and Caputo, G. A. "Antimicrobial polymers as synthetic mimics of host-defense peptides." WIREs Nanomed. Nanobiotechnol., 2013, 5(1), 49-66. DOI: 10.1002/wnan.1199. Mizutani, M.; Palermo, E. F.; Thoma, L. M.; Satoh, K.; Kamigaito, M. and Kuroda, K. "Design and Synthesis of Self-Degradable Antibacterial Polymers by Simultaneous Chain- and Step-Growth Radical Copolymerization." Biomacromolecules, 2012, 13(5), 1554. DOI:10.1021/bm300254s. Palermo, E. F.; Vemparala, S. and Kuroda, K. "Cationic Spacer Arm Design Strategy for Control of Antimicrobial Activity and Conformation of Amphiphilic Methacrylate Random Copolymers." Biomacromolecules, 2012, 13(5), 1632. DOI:10.1021/bm300342u. Gibney, K. A.; Sovadinova, I. Lopez, A. I.; Urban, M.; Ridgway, Z.; Caputo, G. A. and Kuroda, K. "Poly(ethylene imine)s as Antimicrobial Agents with Selective Activity." Macromol. Biosci., 2012, 12(9), 1279. DOI:10.1002/mabi.201200052. Sovadinova, I.; Palermo, E. F.; Urban, M.; Mpiga, P.; Caputo, G. A. and Kuroda, K. "Activity and Mechanism of Antimicrobial Peptide-Mimetic Amphiphilic Polymethacrylate Derivatives." Polymers, 2011, 3, 1512.DOI:10.3390/polym3031512. Oda, Y.; Kanaoka, S.; Sato, T.; Aoshima, S. and Kuroda, K. "Block versus Random Amphiphilic Copolymers as Antibacterial Agents." Biomacromolecules, 2011, 12(10), 3581. DOI:10.1021/bm200780. Han, H.; Wu, J.; Avery, C. W.; Mizutani, M.; Jiang, X.; Kamigaito, M.; Chen, Z.; Xi, C. and Kuroda, K. "Immobilization of Amphiphilic Polycations by Catechol Functionality for Antimicrobial Coatings." Langmuir, 2011, 27(7), 4010. DOI:10.1021/la1046904. Zimmerman, L. B.; Worley, B. V.; Palermo, E. F.; Brender, J. R.; Lee, K.; Kuroda, K.; Ramamoorthy, A. and Meyerhoff, M. E. "Absorbance-Based Assay for Membrane Disruption by Antimicrobial Peptides and Synthetic Copolymers Using Pyrroloquinoline Quinone-Loaded Liposomes." Anal. Biochem., 2011, 411, 194. DOI:10.1016/j.ab.2011.01.009. Avery, C. W.; Palermo, E. F.; McLaughlin, A.; Kuroda, K. and Chen, Z. "Investigations of the Interactions between Synthetic Antimicrobial Polymers and Substrate-Supported Lipid Bilayers Using Sum Frequency Generation Vibrational Spectroscopy." Anal. Chem., 2011, 83(4), 1342. DOI: 10.1021/ac1025804. Palermo, E. F.; Lee, D. K.; Ramamoorthy, A. and Kuroda, K. "Role of Cationic Group Structure in Membrane Binding and Disruption by Amphiphilic Copolymers." J. Phys. Chem. B., 2011, 115(2), 366. DOI: 10.1021/jp1083357. Sovadinova, I.;Palermo, E. F.; Huang, R.; Thoma, L. M.; Kuroda, K. "Mechanism of Polymer-Induced Hemolysis: Nanosized Pore Formation and Osmotic Lysis." Biomacromolecules, 2011, 12 (1), 260. DOI: 10.1021/bm1011739. Palermo, E. F. and Kuroda, K. "Structural determinants of antimicrobial activity in polymers which mimic host defense peptides." Appl. Microbiol. Biotechnol., 2010, 87 (5), 1605. DOI: 10.1007/s00253-010-2687-z. Lamboy, J. A.; Arter, J. A.; Knopp, K. A.; Der, D.; Overstreet, C. M.; Palermo, E. F.; Urakami, H.; Yu, T.; Tezgel, O.; Tew, G. N.; Guan, Z.; Kuroda, K. and Weiss, G. A. "Phage Wrapping with Cationic Polymers Eliminates Nonspecific Binding between M13 Phage and High pI Target Proteins." J. Amer. Chem. Soc., 2009, 131(45), 16454. DOI: 10.1021/ja9050873.