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Identification of structure-activity relationships from screening a structurally compact DNA-encoded chemical library.
- Source :
-
Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2015 Mar 23; Vol. 54 (13), pp. 3927-31. Date of Electronic Publication: 2015 Feb 03. - Publication Year :
- 2015
-
Abstract
- Methods for the rapid and inexpensive discovery of hit compounds are essential for pharmaceutical research and DNA-encoded chemical libraries represent promising tools for this purpose. We here report on the design and synthesis of DAL-100K, a DNA-encoded chemical library containing 103 200 structurally compact compounds. Affinity screening experiments and DNA-sequencing analysis provided ligands with nanomolar affinities to several proteins, including prostate-specific membrane antigen and tankyrase 1. Correlations of sequence counts with binding affinities and potencies of enzyme inhibition were observed and enabled the identification of structural features critical for activity. These results indicate that libraries of this type represent a useful source of small-molecule binders for target proteins of pharmaceutical interest and information on structural features important for binding.<br /> (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Subjects :
- DNA Fingerprinting
DNA Probes chemistry
Enzyme Inhibitors chemical synthesis
Enzyme Inhibitors pharmacology
High-Throughput Screening Assays
Humans
Ligands
Prostate-Specific Antigen drug effects
Serum Albumin chemistry
Small Molecule Libraries
Structure-Activity Relationship
Tankyrases antagonists & inhibitors
DNA chemistry
DNA Probes chemical synthesis
Subjects
Details
- Language :
- English
- ISSN :
- 1521-3773
- Volume :
- 54
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- Angewandte Chemie (International ed. in English)
- Publication Type :
- Academic Journal
- Accession number :
- 25650139
- Full Text :
- https://doi.org/10.1002/anie.201410736