Antibiotics-Peptide Conjugates Against Multidrug-resistant Bacterial Pathogens

Title:Antibiotics-Peptide Conjugates Against Multidrug-resistant Bacterial Pathogens

Volume: 18 Issue: 22

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

Affiliation:

• Center for Targeted Drug Delivery, Department of Biomedical and Pharmaceutical Sciences, Chapman University School of Pharmacy, Harry and Diane Rinker Health Science Campus, 9401 Jeronimo Road, Irvine, CA 92618-1908,United States

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

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.

Cite this article as:

David Ajayi Akinwale, Park Eun Shang, Parang Keykavous and Tiwari Kumar Rakesh*, Antibiotics-Peptide Conjugates Against Multidrug-resistant Bacterial Pathogens, Current Topics in Medicinal Chemistry 2018; 18 (22) . https://dx.doi.org/10.2174/1568026619666181129141524