%0 Journal Article %J European Journal of Medicinal Chemistry %D 2018 %T Antibacterial and anti-TB tat-peptidomimetics with improved efficacy and half-life %A Bhosle, Govind S. %A Nawale, Laxman %A Yeware, Amar M. %A Sarkar, Dhiman %A Fernandes, Moneesha %X 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. %B European Journal of Medicinal Chemistry %V 152 %P 358-369 %8 MAY %G eng %3 Foreign %4 4.519 %R 10.1016/j.ejmech.2018.04.039