flexibility

ASINEX has elaborated a library of diverse macrocycles using an effective tool box of synthetic methods. The resulting scaffolds are novel, tremendously diverse, medchem-relevant, macrocyclic frameworks.

Macrocyles tend to be larger than traditional screening molecules which make them perfect discovery tools for targets with shallow or extended binding sites. At the same time, their unique character based on restricted flexibility and ability to form intra-molecular hydrogen bonds allows for design approaches effectively optimizing properties such asaqueous solubility and membrane permeability. Many of these macrocycles have been tested for aqueous and DMSO solubility with cut-offs applied at 10 mM in DMSO and 50 µM in PBS (pH 7.4) followed by PAMPA permeability assay.

Cyclic peptides are polypeptide chains taking cyclic ring structure, which exhibit diverse biological activities, such as antibacterial activity, immunosuppressive activity and anti-tumor activity. Cyclic peptides, with the features of good binding affinity, target selectivity and low toxicity, show great success as therapeutics. Multiple cyclic peptides are currently in clinical use, for examples, gramicidin and tyrocidine with bactericidal activity, cyclosporin A with immunosuppressive activity, and vancomycin with antibacterial activity. Furthermore, cyclic peptides usually have the sufficient size and a balanced conformational flexibility/rigidity for binding to flat protein-protein interaction (PPI) interfaces, which have potential to develop PPI drugs.

MCE offers a unique collection of 97 cyclic peptides, all of which have good bioactivities. MCE Cyclic Peptide Library is a powerful tool for drug discovery and PPI inhibitor screening.

The discovery of hit molecule is a cornerstone of drug development. Among the diverse tools available, DNA-encoded libraries have emerged a revolutionary platform for high-throughput screening. Compared with traditional HTS, DEL features shorter screening processes, lower costs, simpler assays, and larger library capacities.

DEL Construction utilizes split-and-pool synthesis, a combinatorial chemistry approach that involves iterative splitting, reaction, and pooling. This strategy enables rapid, exponential assembly of fragments in minimal steps without the need for individual compound synthesis andassoicicated isolation or purification steps, thus greatly reducing overall costs. The technology enables simultaneous affinity screeningof massive compound collections to target proteins in a single step. By coupling chemical structures with unique DNA barcodes, each compound is tagged with a distinct DNA sequence for convenient tracking and decoding.DELs readily enable the construction and efficient screening of libraries containing millions to billions of compounds. As a result, DEL screening combines the dual advantages of high efficiency and low cost, making DEL a transformative technology in modern drug discovery.

The DEL kit consists of 50 independent libraries with a total scale of 100 billion compounds. It is constructed through stepwise combinatorial chemistry strategies involving 2-, 3-, and 4-round synthesis. By employing diverse scaffolds and flexible linking strategies, it encompasses various ring systems, linear frameworks, and heterocyclic structures. Screening can be achieved solely through affinity, independent of target-specific activity detection methods. This library is suitable for DEL screening against a wide range of targets.

Recently, significant advancements in tyrosine-targeting electrophiles have primarily occurred in the field of protein-protein interactions (PPIs), where cysteine residues are often underrepresented and novel chemistries are needed to address these interfaces. In this context, tyrosines are frequently more accessible compared to more buried binding sites. Moreover, they are commonly found at "hot spots," which are functional epitopes of PPIs, with 12.3% of the residues consisting of tyrosines. This prevalence is likely due to the hydrophobic nature of tyrosine, its ability to participate in aromatic π-interactions, and its capacity for hydrogen bonding. Beyond PPIs, some progress has also been made in covalent tyrosine targeting in other areas where more commonly addressed side chains are lacking. Even though tyrosine has a slightly lower pKa value compared to the protonated lysine side chain (approximately 10 vs. 10.5 for the unprotected amino acid side chains), significantly less progress has been made in the development of tyrosine-targeted covalent ligands compared to lysine. This is likely due to the reduced flexibility of the tyrosine side chain and the greater steric hindrance of its hydroxy group, which makes it more challenging to adopt suitable reaction geometries.

Through careful selection, we constructed a structural filter containing over 110 electrophilic groups. By analyzing the electrophilic fragments selected by the structural filter, we removed any molecules with trivial or undesirable structural features. Ultimately, we obtained 124 fragment molecules which can target tyrosine residue and can be used for fragment-based covalent drug discovery.

In contrast to the high conservation of conventional orthosteric sites, allosteric sites possess structural characteristics of low conservation, high hydrophobicity, weak polarity, confined spatial geometry, and dynamic cryptic properties. There is a significant difference between their core structures and orthosteric pockets — allosteric pockets are mostly dynamic grooves formed by protein conformational changes, subunit interface clefts, or shallow depressions, rather than the rigid "keyhole" structure of orthosteric sites. With looser spatial constraints, allosteric sites have the advantages of high selectivity and low off-target risk, and have become an important direction in new drug discovery.

Based on the dynamic, hydrophobic, and narrow-long spatial characteristics of allosteric pockets, MCE has performed targeted modification and screening of fragments. The screening criteria strictly conform to the requirements of allosteric binding: molecular weight is controlled at 120–280 Da (to meet the core needs of small molecules in fragment libraries and high derivatization), hydrogen bond donors (HBD ≤ 2), hydrogen bond acceptors (HBA ≤ 3), polar surface area (PSA = 30–80 Ų), rotatable bonds (≤ 2), moderate hydrophobicity (cLogP = 1–3.5), no strongly ionizable groups, and both appropriate rigidity and conformational flexibility to adapt to the dynamic changes of the pocket. Meanwhile, combined with the results of principal moment of inertia (PMI) analysis, fragments with high 3D diversity were obtained. Such fragments have good shape complementarity with allosteric pockets, ensuring that the fragments can smoothly enter the allosteric pockets and form stable binding, while providing room for subsequent optimization and derivation.

This library contains 1,800 structurally diverse fragment molecules with excellent drug-like properties, suitable for allosteric drug development and the design and optimization of allosteric sites. It combines the

MCE Chelating Agarose (IDA) 6FF allows flexible chelation with metal ions such as Zn²⁺, Ni²⁺, or Cu²⁺, and is suitable for the purification of His-tagged recombinant proteins expressed in bacterial, mammalian, insect, and baculovirus systems.

MCE Magnetic Stand Plus features an upgraded design that is compatible with multiple centrifuge tube formats, including 200 μL, 1.5 mL, 2 mL, 5 mL, 10 mL, and 15 mL tubes. It adopts a detachable strong magnetic block design, allowing flexible operation for samples of different volumes and improving both convenience and separation efficiency during experiments.

MCE offers a wide range of multiplex fluorescence kits for simultaneous detection of up to six targets to maximise customer satisfaction (MCE offers six VF series dyes: VF 480, VF 520, VF 570, VF 620, VF 690, and VF 780, allowing customers to flexibly select the appropriate formula based on their specific needs).

MCE offers a wide range of multiplex fluorescence kits for simultaneous detection of up to six targets to maximise customer satisfaction (MCE offers six VF series dyes: VF 480, VF 520, VF 570, VF 620, VF 690, and VF 780, allowing customers to flexibly select the appropriate formula based on their specific needs).

MCE offers a wide range of multiplex fluorescence kits for simultaneous detection of up to six targets to maximise customer satisfaction (MCE offers six VF series dyes: VF 480, VF 520, VF 570, VF 620, VF 690, and VF 780, allowing customers to flexibly select the appropriate formula based on their specific needs).

MCE offers a wide range of multiplex fluorescence kits for simultaneous detection of up to six targets to maximise customer satisfaction (MCE offers six VF series dyes: VF 480, VF 520, VF 570, VF 620, VF 690, and VF 780, allowing customers to flexibly select the appropriate formula based on their specific needs).

MCE offers a wide range of multiplex fluorescence kits for simultaneous detection of up to six targets to maximise customer satisfaction (MCE offers six VF series dyes: VF 480, VF 520, VF 570, VF 620, VF 690, and VF 780, allowing customers to flexibly select the appropriate formula based on their specific needs).

MCE IMAC Agarose (NTA) 6FF is prepared by covalently coupling tetradentate nitrilotriacetic acid (NTA) to an agarose matrix. It features high binding capacity, excellent specificity, and superior ligand stability. The resin allows flexible chelation with metal ions such as Zn²⁺, Ni²⁺, or Cu²⁺, and is suitable for the purification of His-tagged recombinant proteins expressed in bacterial, mammalian, insect, and baculovirus systems.