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Deciphering the Role of Intramolecular Networking in Cholic Acid–Peptide Conjugates on the Lipopolysaccharide Surface in Combating Gram-Negative Bacterial Infections

Published on Feb 28, 2019in Analytical Chemistry6.35
· DOI :10.1021/acs.jmedchem.8b01357
Kavita Yadav3
Estimated H-index: 3
(Manipal University),
Sandeep Kumar4
Estimated H-index: 4
(Manipal University)
+ 15 AuthorsAvinash Bajaj22
Estimated H-index: 22
Abstract
The presence of lipopolysaccharide and emergence of drug resistance make the treatment of Gram-negative bacterial infections highly challenging. Herein, we present the synthesis and antibacterial activities of cholic acid–peptide conjugates (CAPs), demonstrating that valine–glycine dipeptide-derived CAP 3 is the most effective antimicrobial. Molecular dynamics simulations and structural analysis revealed that a precise intramolecular network of CAP 3 is maintained in the form of evolving edges, suggesting intramolecular connectivity. Further, we found high conformational rigidity in CAP 3 that confers maximum perturbations in bacterial membranes relative to other small molecules. Interestingly, CAP 3-coated catheters did not allow the formation of biofilms in mice, and treatment of wound infections with CAP 3 was able to clear the bacterial infection. Our results demonstrate that molecular conformation and internal connectivity are critical parameters to describe the antimicrobial nature of compounds, and...
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#1Rajib Dey (Jawaharlal Nehru Centre for Advanced Scientific Research)
#2Kathakali De (Jawaharlal Nehru Centre for Advanced Scientific Research)
Last.Jayanta Haldar (Jawaharlal Nehru Centre for Advanced Scientific Research)H-Index: 24
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