title: Discovery of antibiotics-derived polymers for gene delivery using combinatorial synthesis and cheminformatics modeling.
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.
authors: Chemical Engineering, Arizona State University, Tempe, AZ 85287-6106, USA.
authors: Thrimoorthy
authors: T
authors: Potta
authors: Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
authors: Zhuo
authors: Z
authors: Zhen
authors: Harrington Biomedical Engineering, Arizona State University, Tempe, AZ 85287, USA.
authors: Taraka Sai Pavan
authors: TS
authors: Grandhi
authors: Chemical Engineering, Arizona State University, Tempe, AZ 85287-6106, USA.
authors: Matthew D
authors: MD
authors: Christensen
authors: Harrington Biomedical Engineering, Arizona State University, Tempe, AZ 85287, USA.
authors: James
authors: J
authors: Ramos
authors: Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
authors: Curt M
authors: CM
authors: Breneman
authors: Chemical Engineering, Arizona State University, Tempe, AZ 85287-6106, USA; Harrington Biomedical Engineering, Arizona State University, Tempe, AZ 85287, USA. Electronic address: kaushal.rege@asu.edu.
authors: Kaushal
authors: K
authors: Rege
mesh_terms: D000617:Aminoglycosides / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques; D018014:Gene Transfer Techniques; D048088:Informatics; D008956:Models, Chemical; D011108:Polymers / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship; D060388:Support Vector Machine
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D011108:Polymers
keywords: Aminoglycosides; Gene delivery; Quantitative structure–Activity relationship (QSAR) models; Rational design