Resistance to Degradation and Cellular Distribution Are Important Features for the Antitumor Activity of Gomesin

Show simple item record

dc.contributor.author Buri, Marcus Vinicius [UNIFESP]
dc.contributor.author Domingues, Tatiana Moreira [UNIFESP]
dc.contributor.author Paredes-Gamero, Edgar Julian [UNIFESP]
dc.contributor.author Casaes-Rodrigues, Rafael L. [UNIFESP]
dc.contributor.author Rodrigues, Elaine Guadelupe [UNIFESP]
dc.contributor.author Miranda, Antonio [UNIFESP]
dc.date.accessioned 2016-01-24T14:34:44Z
dc.date.available 2016-01-24T14:34:44Z
dc.date.issued 2013-11-29
dc.identifier http://dx.doi.org/10.1371/journal.pone.0080924
dc.identifier.citation Plos One. San Francisco: Public Library Science, v. 8, n. 11, 10 p., 2013.
dc.identifier.issn 1932-6203
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/36992
dc.description.abstract Many reports have shown that antimicrobial peptides exhibit anticancer abilities. Gomesin (Gm) exhibits potent cytotoxic activity against cancer cells by a membrane pore formation induced after well-orchestrated intracellular mechanisms. in this report, the replacements of the Cys by Ser or Thr, and the use D-amino acids in the Gm structure were done to investigate the importance of the resistance to degradation of the molecule with its cytotoxicity. [Thr(2,6,11,15)]-Gm, and [Ser(2,6,11,15)]-Gm exhibits low cytotoxicity, and low resistance to degradation, and after 24 h are present in localized area near to the membrane. Conversely, the use of D-amino acids in the analogue [D-Thr(2,6,11,15)]-D-Gm confers resistance to degradation, increases its potency, and maintained this peptide spread in the cytosol similarly to what happens with Gm. Replacements of Cys by Thr and Gln by L- or D-Pro ([D-Thr(2,6,11,15), Pro(9)]-D-Gm, and [Thr(2,6,11,15), D-Pro(9)]-Gm), which induced a similar beta-hairpin conformation, also increase their resistance to degradation, and cytotoxicity, but after 24 h they are not present spread in the cytosol, exhibiting lower cytotoxicity in comparison to Gm. Additionally, chloroquine, a lysosomal enzyme inhibitor potentiated the effect of the peptides. Furthermore, the binding and internalization of peptides was determined, but a direct correlation among these factors was not observed. However, cholesterol ablation, which increase fluidity of cellular membrane, also increase cytotoxicity and internalization of peptides. beta-hairpin spatial conformation, and intracellular localization/target, and the capability of entry are important properties of gomesin cytotoxicity. en
dc.description.sponsorship Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.format.extent 10
dc.language.iso eng
dc.publisher Public Library Science
dc.relation.ispartof Plos One
dc.rights Acesso aberto
dc.title Resistance to Degradation and Cellular Distribution Are Important Features for the Antitumor Activity of Gomesin en
dc.type Artigo
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.description.affiliation Universidade Federal de São Paulo, Dept Biofis, São Paulo, Brazil
dc.description.affiliation Universidade Federal de São Paulo, Dept Bioquim, São Paulo, Brazil
dc.description.affiliation Universidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, São Paulo, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Dept Biofis, São Paulo, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Dept Bioquim, São Paulo, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, São Paulo, Brazil
dc.description.sponsorshipID FAPESP: 2011/17584-0
dc.identifier.file WOS000327670300020.pdf
dc.identifier.doi 10.1371/journal.pone.0080924
dc.description.source Web of Science
dc.identifier.wos WOS:000327670300020



File

Name: WOS000327670300020.pdf
Size: 946.9Kb
Format: PDF
Description:
Open file

This item appears in the following Collection(s)

Show simple item record

Search


Browse

Statistics

My Account