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dc.contributor.authorPolonelli, Luciano
dc.contributor.authorPontón, José
dc.contributor.authorElguezabal Vega, Natalia María
dc.contributor.authorMoragues Tosantos, María Dolores ORCID
dc.contributor.authorCasoli, Claudio
dc.contributor.authorPilotti, Elisabetta
dc.contributor.authorRonzi, Paola
dc.contributor.authorDobroff, Andrey S.
dc.contributor.authorRodrigues, Elaine G.
dc.contributor.authorJuliano, Maria A.
dc.contributor.authorMaffei, Domenico Leonardo
dc.contributor.authorMagliani, Walter
dc.contributor.authorConti, Stefania
dc.contributor.authorTravassos, Luiz R.
dc.date.accessioned2011-06-13T15:20:48Z
dc.date.available2011-06-13T15:20:48Z
dc.date.issued2008-06-11
dc.identifier.citationPLoS ONE 3(6) : (2008) // e2371es
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/10810/4195
dc.description9 p.es
dc.description.abstractBackground: Complementarity-determining regions (CDRs) are immunoglobulin (Ig) hypervariable domains that determine specific antibody (Ab) binding. We have shown that synthetic CDR-related peptides and many decapeptides spanning the variable region of a recombinant yeast killer toxin-like antiidiotypic Ab are candidacidal in vitro. An alanine-substituted decapeptide from the variable region of this Ab displayed increased cytotoxicity in vitro and/or therapeutic effects in vivo against various bacteria, fungi, protozoa and viruses. The possibility that isolated CDRs, represented by short synthetic peptides, may display antimicrobial, antiviral and antitumor activities irrespective of Ab specificity for a given antigen is addressed here. Methodology/Principal Findings: CDR-based synthetic peptides of murine and human monoclonal Abs directed to: a) a protein epitope of Candida albicans cell wall stress mannoprotein; b) a synthetic peptide containing well-characterized B-cell and T-cell epitopes; c) a carbohydrate blood group A substance, showed differential inhibitory activities in vitro, ex vivo and/or in vivo against C. albicans, HIV-1 and B16F10-Nex2 melanoma cells, conceivably involving different mechanisms of action. Antitumor activities involved peptide-induced caspase-dependent apoptosis. Engineered peptides, obtained by alanine substitution of Ig CDR sequences, and used as surrogates of natural point mutations, showed further differential increased/unaltered/decreased antimicrobial, antiviral and/or antitumor activities. The inhibitory effects observed were largely independent of the specificity of the native Ab and involved chiefly germline encoded CDR1 and CDR2 of light and heavy chains. Conclusions/Significance: The high frequency of bioactive peptides based on CDRs suggests that Ig molecules are sources of an unlimited number of sequences potentially active against infectious agents and tumor cells. The easy production and low cost of small sized synthetic peptides representing Ig CDRs and the possibility of peptide engineering and chemical optimization associated to new delivery mechanisms are expected to give rise to a new generation of therapeutic agents.es
dc.description.sponsorshipDepartment of Education, Universities and Research, Basque Goverment (grant IT-264-07), FAPESP 06/50634-2 grant, São Paulo, Brazil; Istituto Superiore di Sanità, National Research Project on A.I.D.S. (grants 50G.30 and 40D.14, ELVIS Italian Network on LTNP), and the Cariparma Banking Foundation (grant 2004.0190). Funding agencies had no role in the design and development of the research work. LRT and EGR are recipients of a research fellowship from the Brazilian National Research Council (CNPq).es
dc.language.isoenges
dc.publisherPublic Library of Sciencees
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.titleAntibody Complementarity-Determining Regions (CDRs) Can Display Differential Antimicrobial, Antiviral and Antitumor Activitieses
dc.typeinfo:eu-repo/semantics/articlees
dc.rights.holder© 2008 Polonelli et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.es
dc.relation.publisherversionhttp://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0002371es
dc.identifier.doi10.1371/journal.pone.0002371
dc.departamentoesEnfermeríaes_ES
dc.departamentoesInmunología, microbiología y parasitologíaes_ES
dc.departamentoeuErizaintzaes_ES
dc.departamentoeuImmunologia, mikrobiologia eta parasitologiaes_ES
dc.subject.categoriaAGRICULTURAL AND BIOLOGICAL SCIENCES
dc.subject.categoriaMEDICINE
dc.subject.categoriaBIOCHEMISTRY AND MOLECULAR BIOLOGY


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