Amino Acid Derived Macromolecular Architectures with Potential Antibacterial Applications

Mukherjee, Ishita (2018) Amino Acid Derived Macromolecular Architectures with Potential Antibacterial Applications. PhD thesis, Indian Institute of Science Education and Research Kolkata.

PDF (PhD thesis of Ishita Mukherjee (14RS059)) 14RS059_RevisedThesis.pdf - Submitted Version Restricted to Repository staff only Download (9MB)

Abstract

The recent development of numerous drug resistant pathogenic bacteria is caused by excessive use of conventional antibiotics for treatment purposes. High costs for new drug development and stringent approval protocols results in fewer trials of new antimicrobial agents per year. These problems lead to several alternating pathways. Antimicrobial peptides (AMPs) are promising alternatives of conventional antidotes due to their broad-spectrum antibacterial activities originated from anti-inflammatory properties and ability to kill multi drug resistance (MDR) microbes, which can interact directly to bacterial negatively charged cell wall through electrostatic and hydrophobic interactions. Complicated multistep synthesis, high manufacturing costs and easy proteolytic degradation introduced severe difficulties in large scale commercial production of AMPs. Hence, biocompatible cationic amphiphilic polymeric materials mimicking the properties of AMPs have been explored with potent antibacterial activity and low toxicity. Another alternative path to shorten the time of development for new antimicrobial agents is formulation and derivatization of existing antibiotics with modified functional groups or alteration of charge density, solubility, degradability, selectivity, and efficiency. Generally common antidotes kill microorganisms through attacking the genetic components; sometimes modification with polymeric materials might modulate the mechanistic pathway to kill bacteria with increasing efficiency and broadness. Herein we will discuss the generation of new antibacterial polymeric materials via controlled polymerization (reversible additionfragmentation chain transfer (RAFT)) technique and their comparative effect on different bacterial strains. Regulation of variable amino acid side chain, amphiphilicity, polymeric architecture, different matrices, coupled bioactive or biopassive properties on bactericidal effect with proper mechanistic elucidation and finally their potential bioapplications are studied in detail.

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