β-Turn Mimetics Library

Peptidomimetics present organic molecules that mimic the action of peptides, which can resemble peptides structurally but differ significantly in their side chains or molecular backbone. An attractive approach to discovering modulators of protein-protein interactions is to use small molecule mimics of β-turn recognition motifs to mimic key interaction residues. The β-turn is one of the three major secondary structure motifs found in proteins and peptides, and occurs where the polypeptide chain reverses direction. In recent years, mimetics of β-turns have been extensively studied and used to discover compounds that can mimic or disrupt β-turn-mediated recognition events. Designing peptides to mimic the behavior of β-turn is easier because most of the designs are less prone to conformational changes than those for α-helix. Peptidomimetic must interact with proteins in a manner similar to natural ligands.

BOC Sciences has designed a β-turn motifs library by employing a variety of ideal β-turn mimetic scaffold.

Figure 1. β-Sheets with general stabilization and mimicking approaches. (Pelaygimeno, M.; et al. 2015)

Library Design

BOC Sciences supports the following three approaches to design our library:

Target-based approach

• We design a focused compound set targeting selected β-turns such as MEF2-HDAC4, HIV-1 gp41, CD81/CV, Bcl-2/Bcl-xL, etc. After the selection by virtual screening, preferences are set to structures with new chemical types

‘Traditional’ three-residue approach

• Our groups have designed compounds with unusual cores with regular crucial residues that mimic i, i+3/i+4 and i+7 located on a recognition surface which is also called hot spot
• BOC Sciences supports three query models with different types of interactions: π-π stacking, cationic-π and H-bond interactions, and S-π interactions. Among them, the S-π interaction approach aims to fuse polyhydrogenated aza-heterocycles with high Fsp³ character by simulating the interaction between the Bim BH3 domain with Mcl-1 and Bcl-2

Ligand-based approach

• A series of novel chemotypes with close topology to known β-turn mimetics are selected. Shape-based similarity and pharmacophore screening are applied as main tools for the library design
• Unique Fsp³-enriched scaffolds with a ladder-like cyclic skeleton are specifically selected to enhance topological and pharmacophore interactions with the target β-turn motifs

Figure 2. Scaffolds that mimic β-turn conformations. (Pelaygimeno, M.; et al. 2015)

β-Turn Mimetics Library Characteristics

• 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
• All of these compounds with Tanimoto index ≥ 0.85
• Compound cherry-picking service is provided

Figure 3. β-Sheet mimetics: Turn mimetics: L-Pro-D-Pro. (Pelaygimeno, M.; et al. 2015)

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 β-Turn Mimetics Library design at competitive prices for global customers. Personalized and customized services of β-Turn Mimetics 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!