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 language | English |
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Pages (from-to) | 1881-1897 |
Number of pages | 17 |
Journal | Nanomedicine |
Volume | 10 |
Issue number | 12 |
DOIs | |
State | Published - Jul 1 2015 |
Bibliographical note
Publisher Copyright:© 2015 Future Medicine Ltd.
Funding
Funders | Funder number |
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National Institutes of Health (NIH) | U01CA151648 |
National Institute of Biomedical Imaging and Bioengineering | R01EB012135 |
Keywords
- binomial distribution
- bionanotechnology
- drug target
- hexameric ATPase
- nanobiotechnology
- nanomotor
- phi29 viral assembly
ASJC Scopus subject areas
- Bioengineering
- Development
- Biomedical Engineering
- General Materials Science
- Medicine (miscellaneous)