Tachyplesin: Difference between revisions
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== Derivatives or Analogue == | == Derivatives or Analogue == | ||
Among all the existing interactions, the cysteine bridges | Among all the existing interactions, the cysteine bridges were considered as the principal contributors of the hairpin loop structure. To test this, three linear derivatives of TP-I (<scene name='67/671725/1ma4/3'>TPY4</scene>, TPF4 and TPA4) were created, in which the bridging cysteine residues were systematically replaced with tyrosine, phenylalanine, and alanine, respectively<ref name=Laederach>PMID:12369825</ref><ref name=Kushibiki>PMID:24389234</ref>. The linear derivatives of TP-I are mentioned below: | ||
[[Image:Seq TPI.jpg|750px]] | [[Image:Seq TPI.jpg|750px]] | ||
Of | Of these 3 linear derivatives of TP-I, NMR structural investigations had shown that TPA4 was unstructured in solution. Also, TPA4 was inactive in terms of antimicrobial activity. In contrast, TPY4 and TPF4 adapt hairpin loop structure and also retain their antimicrobial properties, typical to TP-I. Therefore, the hairpin properties of the peptide seems to be important for recognition of LPS and its biological activities. | ||
Besides replacement of cysteines, deletions was also performed in TP-I which yielded the surprising result of a hairpin loop that was seen, by NMR structure in LPS, in the <scene name='67/671725/Cdt/1'>Cysteine Deleted Tachyplesin</scene> (CDT). Thus, CTD with sequence NH₂-Lys-Trp-Phe-Arg-Val-Tyr-Arg-Gly-Ile-Tyr-Arg-Arg-Arg-CONH₂ did not have disulphide linkage, but was found to have broad spectrum of bactericidal activity. Specifically, CDT has been demonstrated to markedly inhibit the growth of [http://en.wikipedia.org/wiki/Escherichia_coli <i>Escherichia coli</i>] and [http://en.wikipedia.org/wiki/Listeria_monocytogenes <i>Listeria monocytogenes</i>] akin to TP-I, even with lower minimum inhibitory concentration (MIC) values. | Besides replacement of cysteines, deletions was also performed in TP-I which yielded the surprising result of a hairpin loop that was seen, by NMR structure in LPS, in the <scene name='67/671725/Cdt/1'>Cysteine Deleted Tachyplesin</scene> (CDT). Thus, CTD with sequence NH₂-Lys-Trp-Phe-Arg-Val-Tyr-Arg-Gly-Ile-Tyr-Arg-Arg-Arg-CONH₂ did not have disulphide linkage, but was found to have broad spectrum of bactericidal activity. Specifically, CDT has been demonstrated to markedly inhibit the growth of [http://en.wikipedia.org/wiki/Escherichia_coli <i>Escherichia coli</i>] and [http://en.wikipedia.org/wiki/Listeria_monocytogenes <i>Listeria monocytogenes</i>] akin to TP-I, even with lower minimum inhibitory concentration (MIC) values. | ||