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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 [Formula: see text], 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 q(z), 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.
Document Type
Article
Publication Date
7-1-2015
Digital Object Identifier (DOI)
http://dx.doi.org/10.2217/nnm.15.37
Repository Citation
Shu, Dan; Pi, Fengmei; Wang, Chi; Zhang, Peng; and Guo, Peixuan, "New Approach to Develop Ultra-High Inhibitory Drug Using the Power Function of the Stoichiometry of the Targeted Nanomachine or Biocomplex" (2015). Pharmaceutical Sciences Faculty Publications. 35.
https://uknowledge.uky.edu/ps_facpub/35
Notes/Citation Information
Published in Nanomedicine, v. 10, no. 12, p. 1881-1897.
The document available for download is the authors' post-peer-review final draft of the article.