Antibiotics-Peptide Conjugates Against Multidrug-resistant Bacterial Pathogens

Author(s): Akinwale Ajayi David, Shang Eun Park, Keykavous Parang, Rakesh Kumar Tiwari*

Journal Name: Current Topics in Medicinal Chemistry

Volume 18 , Issue 22 , 2018

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Graphical Abstract:


The menace of multi-drug resistance by bacterial pathogens that are responsible for infectious diseases in humans and animals cannot be over-emphasized. Many bacteria develop resistance to antibiotics by one or more combination of resistance mechanisms namely, efflux pump activation thereby reducing bacteria intracellular antibiotic concentration, synthesizing a protein that protects target site causing poor antibiotic affinity to the binding site, or mutations in DNA and topoisomerase gene coding that alters residues in the binding sites. The ability to use a combination of these resistance mechanisms among others creates a phenomenon known as antimicrobial drug resistance. The development of a new class of antibiotics to address bacterial resistance will require many resources, such as time-consuming effort and high cost associated with commercial risk. Hence, the researchers have adopted a strategic approach to enhance the antibacterial efficacy of existing antibiotics by conjugation or combination of existing antibiotics. A number of peptides have become known as antibacterial, cell-penetrating, or membrane-active agents. Antibiotics-Peptide Conjugates (APCs) are a combination of known antibiotics with a peptide connected through a linker. The rationale is to produce an alternative multifunctional antimicrobial compound that will elicit synergistic antibacterial activities while reducing known shortcomings of antibiotics or peptides, such as cellular penetration, serum instability, cytotoxicity, hemolysis, and instability in high salt conditions. In this review, we overview APCs which are used, as a strategy to combat the menace of multi-drug resistance of bacterial pathogens. Furthermore, we explain the focus area of adopted APC strategies and physicochemical properties data that show how they can be used to improve antibacterial efficacy.

Keywords: Antibiotics, Antimicrobial peptide, Antibiotic-peptide conjugate, Covalent conjugation, AMR, DNA.

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Article Details

Year: 2018
Published on: 10 January, 2019
Page: [1926 - 1936]
Pages: 11
DOI: 10.2174/1568026619666181129141524
Price: $65

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