Tachyplesin: Difference between revisions
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Of thois 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. | Of thois 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 <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. | ||
<b><u> CDT Structure </u></b> | <b><u> CDT Structure </u></b> | ||
CDT, like TP-I, has a β-turn | CDT, like TP-I, has a β-turn with the <scene name='67/671725/Cdtturn/2'>same preserved residues</scene> in its LPS-bound structure. | ||
The β-hairpin topology of CDT is sustained by the <scene name='67/671725/Cdthaipin/2'>unique packing interactions</scene> between the aromatic ring of Trp2 and the side-chain of nonpolar amino acid of Val5 and the cationic side-chain of residue Arg11. | The β-hairpin topology of CDT is sustained by the <scene name='67/671725/Cdthaipin/2'>unique packing interactions</scene> between the aromatic ring of Trp2 and the side-chain of nonpolar amino acid of Val5 and the cationic side-chain of residue Arg11. | ||
Also, there exists close proximity between residues <scene name='67/671725/Cdtnoe/1'>Trp2 and Ile9</scene> which is supported by [http://en.wikipedia.org/wiki/Nuclear_Overhauser_effect nuclear overhauser effects (NOEs)] involving [http://en.wikipedia.org/wiki/Indole indole] ring protons of Trp2 with side-chain proton of Ile9. These packing interactions have rendered an approximate anti-parallel orientation of the hairpin structure of CDT in presence of LPS. | Also, there exists close proximity between residues <scene name='67/671725/Cdtnoe/1'>Trp2 and Ile9</scene> which is supported by [http://en.wikipedia.org/wiki/Nuclear_Overhauser_effect nuclear overhauser effects (NOEs)] involving [http://en.wikipedia.org/wiki/Indole indole] ring protons of Trp2 with side-chain proton of Ile9. These packing interactions have rendered an approximate anti-parallel orientation of the hairpin structure of CDT in presence of LPS. | ||