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|Title:||Synthetic modifications of the immunomodulating peptide thymopentin to confer anti-mycobacterial activity|
|Source:||Wang, Y., Ke, X.-Y., Khara, J.S., Bahety, P., Liu, S., Seow, S.V., Yang, Y.Y., Ee, P.L.R. (2014-03). Synthetic modifications of the immunomodulating peptide thymopentin to confer anti-mycobacterial activity. Biomaterials 35 (9) : 3102-3109. ScholarBank@NUS Repository. https://doi.org/10.1016/j.biomaterials.2013.12.049|
|Abstract:||Effective global control of tuberculosis (TB) is increasingly threatened by the convergence of multidrug-resistant TB and the human immunodeficiency virus (HIV) infection. TB/HIV coinfections exert a tremendous burden on the host's immune system, and this has prompted the clinical use of immunomodulators to enhance host defences as an alternative therapeutic strategy. In this study, we modified the clinically used synthetic immunomodulatory pentapeptide, thymopentin (TP-5, RKDVY), with six arginine residues (RR-6, RRRRRR) at the N- and C-termini to obtain the cationic peptides, RR-11 (RKDVYRRRRRR-NH2) and RY-11 (RRRRRRRKDVY-NH2), respectively. The arginine residues conferred anti-mycobacterial activity to TP-5 in the peptides as shown by effective minimum inhibitory concentrations of 125 mg/L and killing efficiencies of >99.99% against both rifampicin-susceptible and -resistant Mycobacterium smegmatis. The immunomodulatory action of the peptides remained unaffected as shown by their ability to stimulate TNF-α production in RAW 264.7 mouse macrophage cells. A distinct change in surface morphology after peptide treatment was observed in scanning electron micrographs, while confocal microscopy and dye leakage studies suggested bacterial membrane disruption by the modified peptides. The modified peptides were non-toxic and did not cause hemolysis of rat red blood cells up to a concentration of 2000 mg/L. Moreover, RY-11 showed synergism with rifampicin and reduced the effective concentration of rifampicin, while preventing the induction of rifampicin resistance. The synthetic peptides may have a potential application in both immunocompetent and immunocompromised TB patients. © 2013 Elsevier Ltd.|
|Appears in Collections:||Staff Publications|
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