Ligase Focused Screening Library

Ligases are important enzymes in living organisms and can catalyze reactions of linking two macromolecules by creating new chemical bonds. Ligases enable to join two molecules into a single molecule or join the first and last parts of a molecule through a catalyze reaction. These proteins are involved in a diversity of cellular pathways such as protein trafficking, subcellular localization, innate immune response, viral infection, DNA damage response and apoptosis. In addition, the ligase-system also plays an important role in tumorigenesis and cancer development.

To meet the growing demand for new structures for drug discovery projects, BOC Sciences has designed its dedicated ligase focused screening library to generate small-molecule analogs of known ligase inhibitors with high bioactivity for the application in high-throughput screening (HTS) and high-content screening (HCS) programs.

Figure 1. Ligase Detection Reaction (LDR). (Lohman, G)

Library Design

Firstly, our scientists apply a series of reliable databases to obtain a reference set of 20,000 compounds with known ligase blocking activity
These compounds have been pre-filtered to retain only those with moderate and high activity against ligase targets
Then, we have performed a further filtering performance to narrow down the 12,000 active entries on 10,000 unique ligase modulators
Finally, BOC Sciences supports a 2D fingerprint similarity search of the reference set against the HTS compounds collection

The search is carried out against the following ligase enzyme targets:

Acetyl-CoA carboxylase (type 1 and 2)	E3 ubiquitin ligase MDM2
Acyl-CoA synthase	Tumor suppressor p53/oncoprotein Mdm2
AMP-binding enzyme family protein	E3 ubiquitin-protein ligase UHRF1
DNA ligase 1	Inhibitor of apoptosis protein 3
Glutamine synthetase	p53-binding protein Mdm-2
NH(3)-dependent NAD(+) synthetase	Ubiquitin-conjugating enzyme E2 N
Pantothenate synthetase	UDP-N-acetylmuramate-L-alanine ligase
Methionyl-tRNA synthetase	UDP-N-acetylmuramoyl-alanine-D-glutamate ligase
Phenylalanyl-tRNA synthetase alpha chain	UDP-N-acetylmuramoyl-tripeptide-D-alanyl-D-alanine ligase
Lysine-, Proline-, Lysyl-, Cysteine-, Prolyl-tRNA synthetase	UDP-N-acetylmuramoyl-L-alanyl-D-glutamate-2,6-diaminopimelate ligase
SUMO E1/E2 ligase	UDP-N-acetylmuramoylalanine-D-glutamyl-lysine-D-alanyl-D-alanine ligase
Transcription intermediary factor 1-alpha

Ligase Focused Screening Library Characteristics

No PAINS or toxic substances/unwanted functions: filtered by strict ‘Ro5-like’ physicochemical and most stringent in-house structural filters
The combination of ligand-based and structure-based approaches used to design this antiviral library provides cross-validation and a higher degree of accuracy
All PAIN and reactive compounds are excluded from selection by internal filter applications
IC₅₀, Ki ,etc less than 10 μM, inhibition >25%
Confirmed bioactivity and safety via preclinical studies and clinical trials
All of the compounds have been selected by ligand efficacy and predicted binding mode
Structural diversity, significant efficacy, and cellular penetration
Structural document, IC₅₀, and other chemical and biological data are provided
Tanimoto index ≥ 0.85
All compounds are continually updated
Compound cherry-picking service is provided

What We Deliver

Delivered within 2 weeks in any customer-preferred format
Powders, dry films or DMSO solutions formatted in vials, 96 or 384-well plates
All compounds have a minimum purity of 90% assessed by ¹H NMR and HPLC
Analytical data is provided

BOC Sciences provides professional, rapid and high-quality services of Ligase Focused Screening Library design at competitive prices for global customers. Personalized and customized services of Ligase Focused Screening Library design can satisfy any innovative scientific study demands. Our clients have direct access to our staff and prompt feedback to their inquiries. If you are interested in our services, please contact us immediately!

Reference

Lohman, G. Substrate specificity and mismatch discrimination in DNA ligases. New England BioLabs.

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Services Based on the Chemical Library Design Platform

BOC Sciences has rich experience in working with global customers in custom library synthesis of compounds and generating small to medium-sized libraries of target compounds. Our knowledge in generating a large number of target molecules in a remarkably shorter time enables quick biological screenings for affinities. With the target properties in mind, we deliver target molecules, by applying our extensive knowledge in drug discovery.

Our mission is to provide clients with a professional chemical library design platform. Empowered by high-quality services and effective research solutions, we are committed to helping customers achieve effective and successful research goals.