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dc.contributor.authorGesteira, Tarsis Ferreira [UNIFESP]
dc.contributor.authorCoulson-Thomas, Vivien Jane [UNIFESP]
dc.contributor.authorTaunay-Rodrigues, Alessandro [UNIFESP]
dc.contributor.authorOliveira, Vitor [UNIFESP]
dc.contributor.authorThacker, Bryan E.
dc.contributor.authorJuliano, Maria Aparecida [UNIFESP]
dc.contributor.authorPasqualini, Renata
dc.contributor.authorArap, Wadih
dc.contributor.authorTersariol, Ivarne Luis dos Santos [UNIFESP]
dc.contributor.authorNader, Helena Bonciani [UNIFESP]
dc.contributor.authorEsko, Jeffrey D.
dc.contributor.authorPinhal, Maria Aparecida da Silva [UNIFESP]
dc.date.accessioned2016-01-24T14:06:12Z
dc.date.available2016-01-24T14:06:12Z
dc.date.issued2011-02-18
dc.identifierhttp://dx.doi.org/10.1074/jbc.M110.100719
dc.identifier.citationJournal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 286, n. 7, p. 5338-5346, 2011.
dc.identifier.issn0021-9258
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/33470
dc.description.abstractN-Deacetylase-N-sulfotransferase 1 (Ndst1) catalyzes the initial modification of heparan sulfate and heparin during their biosynthesis by removal of acetyl groups from subsets of N-acetylglucosamine units and subsequent sulfation of the resulting free amino groups. in this study, we used a phage display library to select peptides that interact with Ndst1, with the aim of finding inhibitors of the enzyme. the phage library consisted of cyclic random 10-mer peptides expressed in the phage capsid protein pIII. Selection was based on the ability of engineered phage to bind to recombinant murine Ndst1 (mNdst1) and displacement with heparin. Peptides that were enriched through multiple cycles of binding and disassociation displayed two specific sequences, CRGWRGEKIGNC and CNMQALSMPVTC. Both peptides inhibited mNdst1 activity in vitro, however, by distinct mechanisms. the peptide CRGWRGEKIGNC presents a chemokine-like repeat motif (BXX, where B represents a basic amino acid and X is a noncharged amino acid) and binds to heparan sulfate, thus blocking the binding of substrate to the enzyme. the peptide NMQALSMPVT inhibits mNdst1 activity by direct interaction with the enzyme near the active site. the discovery of inhibitory peptides in this way suggests a method for developing peptide inhibitors of heparan sulfate biosynthesis.en
dc.format.extent5338-5346
dc.language.isoeng
dc.publisherAmer Soc Biochemistry Molecular Biology Inc
dc.relation.ispartofJournal of Biological Chemistry
dc.rightsAcesso aberto
dc.titleInhibitory Peptides of the Sulfotransferase Domain of the Heparan Sulfate Enzyme, N-Deacetylase-N-sulfotransferase-1en
dc.typeArtigo
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniv Texas MD Anderson Canc Ctr
dc.contributor.institutionUniv Mogi das Cruzes
dc.contributor.institutionUniv Calif San Diego
dc.description.affiliationUniversidade Federal de São Paulo, Dept Bioquim, BR-04044020 São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Biofis, BR-04044020 São Paulo, Brazil
dc.description.affiliationUniv Texas MD Anderson Canc Ctr, David H Koch Ctr, Houston, TX 77030 USA
dc.description.affiliationUniv Mogi das Cruzes, Ctr Interdisciplinar Invest Bioquim, BR-05508000 São Paulo, Brazil
dc.description.affiliationUniv Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA
dc.description.affiliationUniv Calif San Diego, Biomed Sci Grad Program, San Diego, CA USA
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Bioquim, BR-04044020 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Biofis, BR-04044020 São Paulo, Brazil
dc.identifier.doi10.1074/jbc.M110.100719
dc.description.sourceWeb of Science
dc.identifier.wosWOS:000287230600042


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