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dc.contributor.author
Siano, Alvaro Sebastían
dc.contributor.author
Tonarelli, Georgina Guadalupe
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Larpin, Daniel
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Imaz, María Susana
dc.contributor.author
Alvarez, Claudia
dc.contributor.author
Zerbini, Elsa Virginia
dc.date.available
2019-11-19T23:00:42Z
dc.date.issued
2019-06
dc.identifier.citation
Siano, Alvaro Sebastían; Tonarelli, Georgina Guadalupe; Larpin, Daniel; Imaz, María Susana; Alvarez, Claudia; et al.; Analogues of Human Granulysin as Antimycobacterial Agents; Springer; International Journal Of Peptide Research And Therapeutics; 25; 2; 6-2019; 691-696
dc.identifier.issn
1573-3149
dc.identifier.uri
http://hdl.handle.net/11336/89246
dc.description.abstract
Antimicrobial peptides are essential components of innate defense mechanisms and make promising candidates for novel anti-infective agents. The advantages of these peptides in clinical applications include their potential for broad-spectrum and rapid bactericidal activities, and low propensity for resistance development, whereas possible disadvantages include their high cost, limited stability, and unknown toxicology and pharmacokinetics. Granulysin (Gr) is a cytolytic and proinflammatory molecule expressed by activated human cytotoxic T lymphocytes and natural killer (NK) cells. This paper aims to study bacteriostatic and bactericidal activity against Mycobacterium tuberculosis by synthetic analogues of human Gr between 12 and 26 amino acids (AA) and their acyl derivatives. Considering results of previous studies, five new peptides were designed: a cyclic of 20 AA (Gr-SL1); one of 21 AA (linear) (Gr-SL2), another of 12 AA (cyclic) (Gr-SL3) and two lipopeptides (Gr-SL3-lauric and Gr-SL3-palmitic). Peptides were manually synthesized as C-terminal carboxamides by the solid-phase method following Fmoc chemistry. Gr synthetic analogues were purified by reverse phase HPLC and analyzed by analytical C18RP-HPLC and Maldi Tof. The antimycobacterial activity of synthesized Gr analogues was assessed using a microdilution susceptibility test as described previously. Although peptides studied here had neither higher antimycobacterial activity nor lower toxicity than analogs of human Gr previously evaluated, fresh knowledge concerning the influence of acylation and structural aspects analyzed will optimize the design of novel peptides combining the most favorable aspects for the maintenance of antimycobacterial activity with minimum toxicity.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Springer
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
ACYL DERIVATIVES
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ANTIMICROBIAL PEPTIDES
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GRANULYSIN
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MYCOBACTERIUM TUBERCULOSIS
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Química Orgánica
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Ciencias Químicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Analogues of Human Granulysin as Antimycobacterial Agents
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-10-28T16:51:18Z
dc.journal.volume
25
dc.journal.number
2
dc.journal.pagination
691-696
dc.journal.pais
Alemania
dc.description.fil
Fil: Siano, Alvaro Sebastían. Universidad Nacional del Litoral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Tonarelli, Georgina Guadalupe. Universidad Nacional del Litoral; Argentina
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Fil: Larpin, Daniel. Universidad Nacional del Litoral; Argentina
dc.description.fil
Fil: Imaz, María Susana. Instituto Nacional de Enfermedades Respiratorias Dr. Emilio Coni; Argentina
dc.description.fil
Fil: Alvarez, Claudia. Instituto Nacional de Enfermedades Respiratorias Dr. Emilio Coni; Argentina
dc.description.fil
Fil: Zerbini, Elsa Virginia. Universidad Nacional del Litoral; Argentina. Instituto Nacional de Enfermedades Respiratorias Dr. Emilio Coni; Argentina
dc.journal.title
International Journal Of Peptide Research And Therapeutics
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1007/s10989-018-9715-8
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