Antibacterial and anti-TB tat-peptidomimetics with improved efficacy and half-life
| Title | Antibacterial and anti-TB tat-peptidomimetics with improved efficacy and half-life |
| Publication Type | Journal Article |
| Year of Publication | 2018 |
| Authors | Bhosle, GS, Nawale, L, Yeware, AM, Sarkar, D, Fernandes, M |
| Journal | European Journal of Medicinal Chemistry |
| Volume | 152 |
| Pagination | 358-369 |
| Date Published | MAY |
| Abstract | Non-natural antimicrobial peptides are ideal as next-generation antibiotics because of their ability to circumvent the problems of drug resistance and in vivo instability. We report novel all-alpha- and alpha,gamma-mixed Tat peptide analogues as potential antibacterial and anti-TB agents. These peptides have broad spectrum antibacterial activities against Gram-positive (MICs 0.61 +/- 0.03 to 1.35 +/- 0.21 mu M with the peptide gamma TatM4) and Gram-negative (MICs 0.71 +/- 0.005 to 1.26 +/- 0.02 M with gamma TatM4) bacteria and are also effective against active and dormant forms of Mycobacterium tuberculosis, including strains that are resistant to rifampicin and isoniazid. The introduction of the non-natural amino acids of the study in the Tat peptide analogues results in increased resistance to degradation by proteolysis, significantly increasing their half-life. The peptides appear to inhibit bacteria by a membrane disruption mechanism, and have only a low cytotoxic effect on mammalian cells. (C) 2018 Elsevier Masson SAS. All rights reserved. |
| DOI | 10.1016/j.ejmech.2018.04.039 |
| Type of Journal (Indian or Foreign) | Foreign |
| Impact Factor (IF) | 4.519 |
Divison category:
Organic Chemistry
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