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Squaramide-Based 5'-Phosphate Replacements Bind to the DNA Repair Exonuclease SNM1A.
Dürr, Eva-Maria; Doherty, William; Lee, Sook Y; El-Sagheer, Afaf H; Shivalingam, Arun; McHugh, Peter J; Brown, Tom; McGouran, Joanna F.
Afiliación
  • Dürr EM; School of Chemistry Trinity Biomedical Sciences Institute Trinity College Dublin 152-160 Pearse St. Dublin 2 Ireland.
  • Doherty W; School of Chemistry Trinity Biomedical Sciences Institute Trinity College Dublin 152-160 Pearse St. Dublin 2 Ireland.
  • Lee SY; Department of Oncology Weatherall Institute of Molecular Medicine University of Oxford, John Radcliffe Hospital Oxford OX3 9DS UK.
  • El-Sagheer AH; Department of Chemistry University of Oxford 12 Mansfield Road Oxford OX1 3TA UK.
  • Shivalingam A; Department of Chemistry University of Oxford 12 Mansfield Road Oxford OX1 3TA UK.
  • McHugh PJ; Chemistry Branch, Department of Science and Mathematics Faculty of Petroleum and Mining Engineering, Suez University Suez 43721 Egypt.
  • Brown T; Department of Chemistry University of Oxford 12 Mansfield Road Oxford OX1 3TA UK.
  • McGouran JF; Department of Oncology Weatherall Institute of Molecular Medicine University of Oxford, John Radcliffe Hospital Oxford OX3 9DS UK.
ChemistrySelect ; 3(45): 12824-12829, 2018 Dec 06.
Article en En | MEDLINE | ID: mdl-31414040
Phosphate groups are often crucial to biological activity and interactions of oligonucleotides, but confer poor membrane permeability. In addition, the group's lability to enzymatic hydrolysis is an obstacle to its use in therapeutics and in biological tools. We present the synthesis of N-oxyamide and squaramide modifications at the 5'-end of oligonucleotides as phosphate replacements and their biological evaluation using the 5'-exonuclease SNM1A. The squaryl diamide modification showed minimal recognition as a 5'-phosphate mimic; however, modest inhibition of SNM1A, postulated to occur through metal coordination at the active site, was observed. Their facile incorporation after solid-phase synthesis and recognition by the exonuclease makes squaryl diamides attractive neutral 5'-phosphate replacements for oligonucleotides. This work is the first example of squaryl diamide modifications at the 5'-terminal position of oligonucleotides and of the potential use of modified oligonucleotides to bind to the metal center of SNM1A.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: ChemistrySelect Año: 2018 Tipo del documento: Article Pais de publicación: Alemania
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: ChemistrySelect Año: 2018 Tipo del documento: Article Pais de publicación: Alemania