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

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1881-1897
Number of pages17
JournalNanomedicine
Volume10
Issue number12
DOIs
StatePublished - Jul 1 2015

Bibliographical note

Publisher Copyright:
© 2015 Future Medicine Ltd.

Keywords

  • binomial distribution
  • bionanotechnology
  • drug target
  • hexameric ATPase
  • nanobiotechnology
  • nanomotor
  • phi29 viral assembly

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Materials Science (all)

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