Discovery of antibiotics-derived polymers for gene delivery using combinatorial synthesis and cheminformatics modeling

Thrimoorthy Potta, Zhuo Zhen, Taraka Sai Pavan Grandhi, Matthew D. Christensen, James Ramos, Curt M. Breneman, Kaushal Rege

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

We describe the combinatorial synthesis and cheminformatics modeling of aminoglycoside antibiotics-derived polymers for transgene delivery and expression. Fifty-six polymers were synthesized by polymerizing aminoglycosides with diglycidyl ether cross-linkers. Parallel screening resulted in identification of several lead polymers that resulted in high transgene expression levels in cells. The role of polymer physicochemical properties in determining efficacy of transgene expression was investigated using Quantitative Structure-Activity Relationship (QSAR) cheminformatics models based on Support Vector Regression (SVR) and 'building block' polymer structures. The QSAR model exhibited high predictive ability, and investigation of descriptors in the model, using molecular visualization and correlation plots, indicated that physicochemical attributes related to both, aminoglycosides and diglycidyl ethers facilitated transgene expression. This work synergistically combines combinatorial synthesis and parallel screening with cheminformatics-based QSAR models for discovery and physicochemical elucidation of effective antibiotics-derived polymers for transgene delivery in medicine and biotechnology.

Original languageEnglish (US)
Pages (from-to)1977-1988
Number of pages12
JournalBiomaterials
Volume35
Issue number6
DOIs
StatePublished - Feb 1 2014

    Fingerprint

Keywords

  • Aminoglycosides
  • Gene delivery
  • Quantitative structure-Activity relationship (QSAR) models
  • Rational design

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this