Receptor-based Aspartic Protease Focused Library

Aspartate proteases are an important class of protein hydrolases involved in the metabolic and bioregulatory roles of the body. Aspartate proteases can be widely found in vertebrates, fungi, plants, retroviruses and some plant viruses. Most aspartate proteases have two aspartate residues in their catalytic site, where the nucleophilic reagent that attacks the scissor peptide bond is an activated water molecule. Mammalian aspartic proteases include the digestive enzymes (pepsin and chymotrypsin), the intra-cellular cathespin D and cathespin E, and renin.

BOC Sciences can design a receptor-based aspartic protease focused library based on the docking-based virtual screening protocol.

Figure 1. Structure of a presenilin family intramembrane aspartate protease. (Xiaochun, L.; et al. 2013)

Receptor-based Aspartic Protease Focused Library Design

Renin-angiotensin-aldosterone system (RAAS) blocking has been considered an attractive option for the treatment of hypertension, and many related anti-hypertensive drugs are now on the market. BOC Sciences has developed a novel library of target-based screening compounds for renin, an important representative of aspartate proteases.

• A docking-based virtual screening protocal: the Glide docking program of the Schrödinger software has been used to scan potential renin active site binders (RCSB PDB: 2V0Z, 2IKO, 3OWN and 2X0B) through our HTS compound collection
• Since all the reference structures contain gaps in close proximity to inhibitor site interactions, a full 3D-model of renin is reconstructed, while protein structure preparation is performed using our well-designed algorithms
• No docking constraints are applied to allow the docking algorithm to explore as many ligands’ positions and orientation as possible
• Over 2,300 small-molecule compounds with potential renin-binding activity are generated via in silico screening and filtering through toxic groups/reactive moieties to form the target library presented herein
• In order to not filter out many peptide-mimicking compounds, the library has not been made Ro5 compatible

Receptor-based Aspartic Protease Focused Library Characteristics

• High diversity over the screening set: mean Tanimoto > 0.85
• Favorable physicochemical parameters and solubility requirements
• No PAINS or toxic substances/unwanted functions: filtered by strict ‘Ro5-like’ physicochemical and most stringent in-house structural filters
• Bioactivity and safety confirmed by preclinical studies and clinical trials
• Structural diversity, medicinal activity, and cellular penetration
• Structural document, IC₅₀, and other chemical and biological data are provided
• 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 Receptor-based Aspartic Protease Focused Library design at competitive prices for global customers. Personalized and customized services of Receptor-based Aspartic Protease Focused 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!