Developments with bead-based screening for novel drug discovery
| Autor: | George Appiah Kubi, Dehua Pei |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
Drug discovery Peptidomimetic Computer science High-throughput screening Computational biology Article High-Throughput Screening Assays Small Molecule Libraries 03 medical and health sciences 0302 clinical medicine Peptide Library 030220 oncology & carcinogenesis Expert opinion Drug Discovery Combinatorial Chemistry Techniques Humans 030304 developmental biology |
| Zdroj: | Expert Opin Drug Discov |
| ISSN: | 1746-045X |
| Popis: | Introduction: Combinatorial chemistry provides a cost-effective method for rapid discovery of drug hits/leads. The one-bead-one-compound (OBOC) library method is in principle ideally suited for this application, because it permits a large number of structurally diverse compounds to be rapidly synthesized and simultaneously screened for binding to a target of interest. However, application of OBOC libraries in drug discovery has encountered significant technical challenges. Areas covered: This Special Report covers the challenges associated with first-generation OBOC libraries (difficulty in structural identification of non-peptidic hits, screening biases and high false positive rates, and poor scalability). It also covers the many strategies developed over the past two decades to overcome these challenges. Expert opinion: With most of the technical challenges now overcome and the advent of powerful intracellular delivery technologies, OBOC libraries of metabolically stable and conformationally rigidified molecules (macrocyclic peptides and peptidomimetics, rigidified acyclic oligomers, and D-peptides) can be routinely synthesized and screened to discover initial hits against previously undruggable targets such as intracellular protein-protein interactions. On the other hand, further developments are still needed to expand the utility of the OBOC method to non-peptidic chemical scaffolds. |
| Databáze: | OpenAIRE |
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