Inhibitory Peptides of the Sulfotransferase Domain of the Heparan Sulfate Enzyme, N-Deacetylase-N-sulfotransferase-1
Autor(a) principal: | |
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Data de Publicação: | 2011 |
Outros Autores: | , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/33470 http://dx.doi.org/10.1074/jbc.M110.100719 |
Resumo: | N-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. |
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Gesteira, Tarsis Ferreira [UNIFESP]Coulson-Thomas, Vivien Jane [UNIFESP]Taunay-Rodrigues, Alessandro [UNIFESP]Oliveira, Vitor [UNIFESP]Thacker, Bryan E.Juliano, Maria Aparecida [UNIFESP]Pasqualini, RenataArap, WadihTersariol, Ivarne Luis dos Santos [UNIFESP]Nader, Helena Bonciani [UNIFESP]Esko, Jeffrey D.Pinhal, Maria Aparecida da Silva [UNIFESP]Universidade Federal de São Paulo (UNIFESP)Univ Texas MD Anderson Canc CtrUniv Mogi das CruzesUniv Calif San Diego2016-01-24T14:06:12Z2016-01-24T14:06:12Z2011-02-18Journal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 286, n. 7, p. 5338-5346, 2011.0021-9258http://repositorio.unifesp.br/handle/11600/33470http://dx.doi.org/10.1074/jbc.M110.10071910.1074/jbc.M110.100719WOS:000287230600042N-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.Universidade Federal de São Paulo, Dept Bioquim, BR-04044020 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biofis, BR-04044020 São Paulo, BrazilUniv Texas MD Anderson Canc Ctr, David H Koch Ctr, Houston, TX 77030 USAUniv Mogi das Cruzes, Ctr Interdisciplinar Invest Bioquim, BR-05508000 São Paulo, BrazilUniv Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USAUniv Calif San Diego, Biomed Sci Grad Program, San Diego, CA USAUniversidade Federal de São Paulo, Dept Bioquim, BR-04044020 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biofis, BR-04044020 São Paulo, BrazilWeb of Science5338-5346engAmer Soc Biochemistry Molecular Biology IncJournal of Biological ChemistryInhibitory Peptides of the Sulfotransferase Domain of the Heparan Sulfate Enzyme, N-Deacetylase-N-sulfotransferase-1info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP11600/334702022-02-18 10:09:37.829metadata only accessoai:repositorio.unifesp.br:11600/33470Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652022-02-18T13:09:37Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Inhibitory Peptides of the Sulfotransferase Domain of the Heparan Sulfate Enzyme, N-Deacetylase-N-sulfotransferase-1 |
title |
Inhibitory Peptides of the Sulfotransferase Domain of the Heparan Sulfate Enzyme, N-Deacetylase-N-sulfotransferase-1 |
spellingShingle |
Inhibitory Peptides of the Sulfotransferase Domain of the Heparan Sulfate Enzyme, N-Deacetylase-N-sulfotransferase-1 Gesteira, Tarsis Ferreira [UNIFESP] |
title_short |
Inhibitory Peptides of the Sulfotransferase Domain of the Heparan Sulfate Enzyme, N-Deacetylase-N-sulfotransferase-1 |
title_full |
Inhibitory Peptides of the Sulfotransferase Domain of the Heparan Sulfate Enzyme, N-Deacetylase-N-sulfotransferase-1 |
title_fullStr |
Inhibitory Peptides of the Sulfotransferase Domain of the Heparan Sulfate Enzyme, N-Deacetylase-N-sulfotransferase-1 |
title_full_unstemmed |
Inhibitory Peptides of the Sulfotransferase Domain of the Heparan Sulfate Enzyme, N-Deacetylase-N-sulfotransferase-1 |
title_sort |
Inhibitory Peptides of the Sulfotransferase Domain of the Heparan Sulfate Enzyme, N-Deacetylase-N-sulfotransferase-1 |
author |
Gesteira, Tarsis Ferreira [UNIFESP] |
author_facet |
Gesteira, Tarsis Ferreira [UNIFESP] Coulson-Thomas, Vivien Jane [UNIFESP] Taunay-Rodrigues, Alessandro [UNIFESP] Oliveira, Vitor [UNIFESP] Thacker, Bryan E. Juliano, Maria Aparecida [UNIFESP] Pasqualini, Renata Arap, Wadih Tersariol, Ivarne Luis dos Santos [UNIFESP] Nader, Helena Bonciani [UNIFESP] Esko, Jeffrey D. Pinhal, Maria Aparecida da Silva [UNIFESP] |
author_role |
author |
author2 |
Coulson-Thomas, Vivien Jane [UNIFESP] Taunay-Rodrigues, Alessandro [UNIFESP] Oliveira, Vitor [UNIFESP] Thacker, Bryan E. Juliano, Maria Aparecida [UNIFESP] Pasqualini, Renata Arap, Wadih Tersariol, Ivarne Luis dos Santos [UNIFESP] Nader, Helena Bonciani [UNIFESP] Esko, Jeffrey D. Pinhal, Maria Aparecida da Silva [UNIFESP] |
author2_role |
author author author author author author author author author author author |
dc.contributor.institution.none.fl_str_mv |
Universidade Federal de São Paulo (UNIFESP) Univ Texas MD Anderson Canc Ctr Univ Mogi das Cruzes Univ Calif San Diego |
dc.contributor.author.fl_str_mv |
Gesteira, Tarsis Ferreira [UNIFESP] Coulson-Thomas, Vivien Jane [UNIFESP] Taunay-Rodrigues, Alessandro [UNIFESP] Oliveira, Vitor [UNIFESP] Thacker, Bryan E. Juliano, Maria Aparecida [UNIFESP] Pasqualini, Renata Arap, Wadih Tersariol, Ivarne Luis dos Santos [UNIFESP] Nader, Helena Bonciani [UNIFESP] Esko, Jeffrey D. Pinhal, Maria Aparecida da Silva [UNIFESP] |
description |
N-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. |
publishDate |
2011 |
dc.date.issued.fl_str_mv |
2011-02-18 |
dc.date.accessioned.fl_str_mv |
2016-01-24T14:06:12Z |
dc.date.available.fl_str_mv |
2016-01-24T14:06:12Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Journal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 286, n. 7, p. 5338-5346, 2011. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/33470 http://dx.doi.org/10.1074/jbc.M110.100719 |
dc.identifier.issn.none.fl_str_mv |
0021-9258 |
dc.identifier.doi.none.fl_str_mv |
10.1074/jbc.M110.100719 |
dc.identifier.wos.none.fl_str_mv |
WOS:000287230600042 |
identifier_str_mv |
Journal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 286, n. 7, p. 5338-5346, 2011. 0021-9258 10.1074/jbc.M110.100719 WOS:000287230600042 |
url |
http://repositorio.unifesp.br/handle/11600/33470 http://dx.doi.org/10.1074/jbc.M110.100719 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.none.fl_str_mv |
Journal of Biological Chemistry |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
5338-5346 |
dc.publisher.none.fl_str_mv |
Amer Soc Biochemistry Molecular Biology Inc |
publisher.none.fl_str_mv |
Amer Soc Biochemistry Molecular Biology Inc |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
instacron_str |
UNIFESP |
institution |
UNIFESP |
reponame_str |
Repositório Institucional da UNIFESP |
collection |
Repositório Institucional da UNIFESP |
repository.name.fl_str_mv |
Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
repository.mail.fl_str_mv |
|
_version_ |
1802764105624322048 |