Our DSI Poised Fragment Library is an original collection of 2,300 synthetically versatile, high-quality fragments for Fragment-Based Drug Discovery (FBDD). Built upon the concept of poised chemistry introduced by the Diamond Light Source (DSI) and Structural Genomics Consortium (SGC), this screening Library provides medicinal chemists and structural biologists with a powerful platform for rapid hit elaboration and efficient structure-activity relationship (SAR) exploration.
Key Advantages
- Synthetically tractable fragments containing at least one poised bond that can be easily modified through reliable, well-characterized reactions, such as amide coupling, Suzuki-type aryl–aryl coupling, and reductive amination
- Compact, synthetically “poised” substructures ready for parallel chemistry expansion and derivatization
- Streamlined hit optimization: poised scaffolds enable quick analog synthesis, facilitating iterative design-synthesize-test cycles for lead generation
- Balanced physicochemical parameters with focus on solubility, stability for robust screening performance coupled with high binding efficiency
- Structurally diverse, non-redundant scaffolds suitable for NMR, SPR, X-ray, and other biophysical fragment screening techniques [2]
- Validated quality and purity: all compounds are sourced from the proprietary HTS Compound Collection, with a purity of over 90 %, confirmed by NMR and/or LC-MS
Representative screening compounds from the Screening Library
The DSI Poised Fragment Library is ideal for
- Fragment screening campaigns targeting challenging or novel proteins
- Structure-based design and ligand-efficient lead generation SAR expansion and analog synthesis through poised bond chemistry
- Integration with crystallography and biophysical assays for rapid validation
Life Chemicals provides a unique combination of cheminformatics expertise and synthetic capability, allowing customers to:
- Order synthesis of individual molecules, custom-tailored sets and subsets, as well as ready-to-screen libraries
- Access solid or DMSO formats in multiple plate layouts
- Obtain analogue design support for poised fragment elaboration
The compound selection can be customized to meet your specific requirements. Cherry-picking is available.
Please, contact us at orders@lifechemicals.com for any additional information and price quotations.
Library Design and Fragment Selection
Selecting compounds, we prioritized fragments with balanced lipophilicity (cLogP < 3), low molecular weight (150–300 Da), optimal rotatable bond count, balanced H-bond donor/acceptor counts, and minimal conformational flexibility to maximize ligand efficiency and target engagement. The inclusion of hydrogen bond donors and acceptors promotes strong interactions with target proteins, making the fragments well-suited for efficient hit-to-lead progression.
The Library design integrates advanced cheminformatics filtering and drug-likeness profiling to ensure both chemical diversity and synthetic accessibility. Compounds were filtered using REOS and PAINS algorithms within the Schrödinger suite, eliminating reactive, unstable, or non-specific structures [1]. Non-ring fragments were excluded to maintain 3D shape complementarity, and BBB permeability and CNS MPO scoring were used, where relevant, to optimize physicochemical balance.
Figure 1. Compound selection workflow and examples of selected poised fragments
Reference:
- Kralj, S.; Jukič, M.; Bren, U. Comparative Analyses of Medicinal Chemistry and Cheminformatics Filters with Accessible Implementation in Konstanz Information Miner (KNIME). Int. J. Mol. Sci.2022, 23, 5727. https://doi.org/10.3390/ijms23105727.
- Lamoree B, Hubbard RE. Using Fragment-Based Approaches to Discover New Antibiotics. SLAS Discov. 2018;23(6):495-510. doi:10.1177/2472555218773034.