Your browser doesn't support javascript.
loading
Small molecule mimetics of an interferon-α receptor interacting domain.
Bello, Angelica M; Wei, Lianhu; Majchrzak-Kita, Beata; Salum, Noruê; Purohit, Meena K; Fish, Eleanor N; Kotra, Lakshmi P.
Afiliación
  • Bello AM; Center for Molecular Design and Preformulations, University Health Network, Toronto, Ontario M5G 1L7, Canada; Toronto General Research Institute, Toronto, Ontario M5G 2M1, Canada; Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.
  • Wei L; Center for Molecular Design and Preformulations, University Health Network, Toronto, Ontario M5G 1L7, Canada; Toronto General Research Institute, Toronto, Ontario M5G 2M1, Canada; Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.
  • Majchrzak-Kita B; Toronto General Research Institute, Toronto, Ontario M5G 2M1, Canada.
  • Salum N; Center for Molecular Design and Preformulations, University Health Network, Toronto, Ontario M5G 1L7, Canada; Federal University of Paraná, Curitiba, Paraná, Brazil.
  • Purohit MK; Center for Molecular Design and Preformulations, University Health Network, Toronto, Ontario M5G 1L7, Canada; Department of Pharmacy, Birla Institute of Technology & Science, Pilani 333 031, India.
  • Fish EN; Toronto General Research Institute, Toronto, Ontario M5G 2M1, Canada; Department of Immunology, University of Toronto, Toronto, Canada.
  • Kotra LP; Center for Molecular Design and Preformulations, University Health Network, Toronto, Ontario M5G 1L7, Canada; Toronto General Research Institute, Toronto, Ontario M5G 2M1, Canada; Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada;
Bioorg Med Chem ; 22(3): 978-85, 2014 Feb 01.
Article en En | MEDLINE | ID: mdl-24433965
Small molecules that mimic IFN-α epitopes that interact with the cell surface receptor, IFNAR, would be useful therapeutics. One such 8-amino acid region in IFN-α2, designated IRRP-1, was used to derive 11 chemical compounds that belong to 5 distinct chemotypes, containing the molecular features represented by the key residues Leu30, Arg33, and Asp35 in IRRP-1. Three of these compounds exhibited potential mimicry to IRRP-1 and, in cell based assays, as predicted, effectively inhibited IFNAR activation by IFN-α. Of these, compound 3 did not display cell toxicity and reduced IFN-α-inducible STAT1 phosphorylation and STAT-DNA binding. Based on physicochemical properties' analyses, our data suggest that moieties with acidic pKa on the small molecule may be a necessary element for mimicking the carboxyl group of Asp35 in IRRP-1. Our data confirm the relevance of this strategy of molecular mimicry of ligand-receptor interaction domains of protein partners for small molecule drug discovery.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptor de Interferón alfa y beta / Bibliotecas de Moléculas Pequeñas / Epítopos Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Bioorg Med Chem Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2014 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptor de Interferón alfa y beta / Bibliotecas de Moléculas Pequeñas / Epítopos Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Bioorg Med Chem Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2014 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido