High-affinity A/T-rich DNA binding with a dimeric bisbenzamidine

  1. Bouzada, David 2
  2. Paul, Ananya 3
  3. Sánchez, Mateo I 2
  4. Domínguez-Asenjo, Bárbara 56
  5. Lence, Emilio 2
  6. Melle-Franco, Manuel 4
  7. Ardá, Ana 1
  8. Barreiro-Piñeiro, Natalia 7
  9. Penas, Cristina 2
  10. Gómez-González, Jacobo 2
  11. Jiménez-Barbero, Jesús 1
  12. Moreno, Javier 56
  13. González-Bello, Concepción 2
  14. Wilson, W David 3
  15. Mascareñas, José L 2
  16. Vázquez, M Eugenio 2
  1. 1 CIC bioGUNE, Basque Research & Technology Alliance (BRTA), Bizkaia Technology Park , Building 800, 48162 Derio, Bizkaia ,
  2. 2 Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CiQUS), Departamento de Química Orgánica, Universidade de Santiago de Compostela , Santiago de Compostela 15782 ,
  3. 3 Department of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University , Atlanta, GA 30303 ,
  4. 4 CICECO - Aveiro Institute of Materials, Department of Chemistry, University of Aveiro , Aveiro 3810-193 ,
  5. 5 WHO Collaborating Centre for Leishmaniasis, National Centre for Microbiology Instituto de Salud Carlos III , Madrid ,
  6. 6 Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFECT), Instituto de Salud Carlos III , Madrid ,
  7. 7 Group of Molecular Virology, Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CiQUS), Departamento de Bioquímica e Bioloxía Molecular, Universidade de Santiago de Compostela , Santiago de Compostela, 15782 ,
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Revista:
NAR Molecular Medicine

ISSN: 2976-856X

Ano de publicación: 2024

Volume: 1

Número: 4

Tipo: Artigo

DOI: 10.1093/NARMME/UGAE022 GOOGLE SCHOLAR lock_openAcceso aberto editor

Outras publicacións en: NAR Molecular Medicine

Resumo

A bisbenzamidine DNA binding agent can be easily dimerized by alkylation of its terminal amidine groups to afford an extended minor groove binder with over 20-fold enhanced DNA affinity toward extended A/T-rich sites. Nuclear magnetic resonance experiments in combination with molecular dynamics simulation studies provide structural insight into the insertion of this compound in the DNA minor groove, and antimicrobial assays demonstrate that the increased affinity translates into higher antileishmanial activity.