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Identification and insertion of 3-carbon bridges in protein disulfide bonds: a computational approach.
Zloh, Mire; Shaunak, Sunil; Balan, Sibu; Brocchini, Steve.
Afiliación
  • Zloh M; Department of Pharmaceutical and Biological Chemistry, University of London, 29/39 Brunswick Square, London WC1N 1AX, UK. mire.zloh@pharmacy.ac.uk
Nat Protoc ; 2(5): 1070-83, 2007.
Article en En | MEDLINE | ID: mdl-17545999
More than 42,000 3D structures of proteins are available on the Internet. We have shown that the chemical insertion of a 3-carbon bridge across the native disulfide bond of a protein or peptide can enable the site-specific conjugation of PEG to the protein without a loss of its structure or function. For success, it is necessary to select an appropriate and accessible disulfide bond in the protein for this chemical modification. We describe how to use public protein databases and molecular modeling programs to select a protein rationally and to identify the optimum disulfide bond for experimental studies. Our computational approach can substantially reduce the time required for the laboratory-based chemical modification. Identification of solvent-accessible disulfides using published structural information takes approximately 2 h. Predicting the structural effects of the disulfide-based modification can take 3 weeks.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Conformación Proteica / Carbono / Proteínas / Modelos Moleculares / Química Física / Biología Computacional / Disulfuros Tipo de estudio: Diagnostic_studies / Prognostic_studies Idioma: En Revista: Nat Protoc Año: 2007 Tipo del documento: Article Pais de publicación: Reino Unido
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Conformación Proteica / Carbono / Proteínas / Modelos Moleculares / Química Física / Biología Computacional / Disulfuros Tipo de estudio: Diagnostic_studies / Prognostic_studies Idioma: En Revista: Nat Protoc Año: 2007 Tipo del documento: Article Pais de publicación: Reino Unido