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An efficient strategy to enhance binding affinity and specificity of a known isozyme inhibitor.
Jee, Joo-Eun; Lim, Jaehong; Ong, Yong Siang; Oon, Jessica; Gao, Liqian; Choi, Hak Soo; Lee, Su Seong.
Afiliação
  • Jee JE; Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore. sslee@ibn.a-star.edu.sg.
  • Lim J; Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore. sslee@ibn.a-star.edu.sg.
  • Ong YS; Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore. sslee@ibn.a-star.edu.sg.
  • Oon J; Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore. sslee@ibn.a-star.edu.sg.
  • Gao L; Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore. sslee@ibn.a-star.edu.sg.
  • Choi HS; Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, White 427, Boston, MA 02114, USA. hchoi12@mgh.harvard.edu.
  • Lee SS; Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore. sslee@ibn.a-star.edu.sg.
Org Biomol Chem ; 14(28): 6833-9, 2016 Jul 12.
Article em En | MEDLINE | ID: mdl-27339902
The binding profile of a known inhibitor, benzenesulfonamide, against a family of carbonic anhydrase isozymes was efficiently enhanced via high-throughput screening of customized combinatorial one-bead-one-compound peptide libraries modified with the inhibitor molecule. The screening of the conjugate libraries recognized subtle variations in the microenvironments of the target enzyme and thus facilitated the identification of short peptide sequences that bind selectively to a close proximity of the active site. The identified peptide portions contributed significantly to the overall binding of the conjugate peptides with greatly enhanced affinity as well as improved specificity towards the target isozyme. The interactions between the inhibitors and the isozymes were validated by surface plasmon resonance (SPR), pull-down assay and enzymatic activity measurement. This high-throughput approach proved useful and efficient to enhance the binding profile of known inhibitors and may apply to developing effective inhibitors for a wide range of isozyme families.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Peptídeos / Sulfonamidas / Inibidores da Anidrase Carbônica / Anidrases Carbônicas Limite: Humans Idioma: En Revista: Org Biomol Chem Assunto da revista: BIOQUIMICA / QUIMICA Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Singapura

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Peptídeos / Sulfonamidas / Inibidores da Anidrase Carbônica / Anidrases Carbônicas Limite: Humans Idioma: En Revista: Org Biomol Chem Assunto da revista: BIOQUIMICA / QUIMICA Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Singapura