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New approach to develop ultra-high inhibitory drug using the power function of the stoichiometry of the targeted nanomachine or biocomplex

  • Dan Shu
  • , Fengmei Pi
  • , Chi Wang
  • , Peng Zhang
  • , Peixuan Guo

Producción científica: Articlerevisión exhaustiva

14 Citas (Scopus)

Resumen

Aims: To find methods for potent drug development by targeting to biocomplex with high copy number. Methods: Phi29 DNA packaging motor components with different stoichiometries were used as model to assay virion assembly with Yang Hui's Triangle , where Z = stoichiometry, M = drugged subunits per biocomplex, p and q are the fraction of drugged and undrugged subunits in the population. Results: Inhibition efficiency follows a power function. When number of drugged subunits to block the function of the complex K = 1, the uninhibited biocomplex equals qz, demonstrating the multiplicative effect of stoichiometry on inhibition with stoichiometry 1000 > 6 > 1. Complete inhibition of virus replication was found when Z = 6. Conclusion: Drug inhibition potency depends on the stoichiometry of the targeted components of the biocomplex or nanomachine. The inhibition effect follows a power function of the stoichiometry of the target biocomplex.

Idioma originalEnglish
Páginas (desde-hasta)1881-1897
Número de páginas17
PublicaciónNanomedicine
Volumen10
N.º12
DOI
EstadoPublished - jul 1 2015

Nota bibliográfica

Publisher Copyright:
© 2015 Future Medicine Ltd.

Financiación

FinanciadoresNúmero del financiador
National Institutes of Health (NIH)U01CA151648
National Institute of Biomedical Imaging and BioengineeringR01EB012135

    ASJC Scopus subject areas

    • Bioengineering
    • Development
    • Biomedical Engineering
    • General Materials Science
    • Medicine (miscellaneous)

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