Advances in high-throughput screening: better compounds, novel targets, enhanced sensors

High throughput screening (HTS) is the dominant force in modern drug discovery. Through the evaluation of large structure collections, novel drug leads can be rapidly assessed for modulation of medicinally-relevant biological targets. This occurs through the interplay of three intrinsically linked facets, namely A) the chemical collections being screened, B) the biomolecular targets against which the compounds are assayed, and C) the technologies employed in the screening process. In this multipronged treatment, each of the three above mentioned concepts will be explored. Chapter 2 will explore chemoinformatics methods for quantifying structural complexity and diversity in large screening libraries. Chapter 3 will describe an optical biosensor-based assay for inhibitors of the RNA-protein binding interaction responsible for type 1 myotonic dystrophy (DM1), a hereditary degenerative disorder. Finally, Chapter 4 will explore the limits of small-molecule detection in a novel laser-based optical biosensor technology. Taken together, these three stories encompass the full range of HTS concepts and offer a glimpse into the future of drug discovery.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2013

Author dc:creator

• Flood, Timothy

Contributors dc:contributor

• Hergenrother, Paul J.
• Zimmerman, Steven C.
• Cunningham, Brian T.
• Baranger, Anne M.

• myotonic dystrophy
• high-throughput screening (HTS)
• drug discovery
• natural products
• chemical diversity
• screening collections
• chemoinformatics
• cheminformatics
• Tanimoto similarity
• molecular properties
• RNA
• RNA binding
• type 1 myotonic dystrophy (DM1)
• MBNL1
• biomolecular interactions
• biosensors
• protein-ligand interactions
• estrogen receptor
• estradiol
• external cavity laser
• photonic crystal
• X-linked inhibitor of apoptosis protein (XIAP)
• SM-164

Statement dc:rights

• Copyright 2013 Timothy A. Flood, Jr.

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/44780

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/44780