PPI Helix Turn 3D-Mimetics Library

PPI are the most screened target class in high-throughput screening (HTS). However, most commercially available chemical libraries are not suitable for screening PPI targets as the success rate of finding hit compounds in many HTS campaigns using small molecule compounds usually remains very low. The PPI inhibitors discovered so far are significantly different compared to most known drugs: they are typically larger, more hydrophobic, contain more (heterogeneous) aromatic rings, and therefore belong to "beyond Ro5" chemical space. In recent years, compounds with diverse and well-developed 3D shapes have gained the most attractiveness.

In view of this, BOC Sciences is committed to designing a PPI-focused library to achieve a suitable chemical space. We have introduced the Fsp³ parameter as an important measure of molecular three-dimensionality and complexity for libraries members.

Figure 1. Translation of α-helix peptides into α-helix mimetics. (Rosario, M. 2017)

PPI Helix Turn 3D-Mimetics Library Design

This library is designed based on selected sp³-enriched scaffolds from our DOS chemistry and populated with members that are able to mimic α-helices and β-turns as key recognition elements of protein secondary structure.

The following requirements are applied for preferable scaffolds selection:

• Mimicry of helix by the structure of polycyclic small molecule scaffolds
• Mimicry of side-chain residues on one face of the α-helix
• At least three points of interaction with 7-ala helix
• Possible H-bond, hydrophobic, electrostatic
• Include hydrophilic regions in the scaffolds
• Avoidance of polycyclic aromatics (such as terphenyls and their hetero-analogs, oligobenzamides and their hetero-analogs)
• High Fsp³ for core scaffolds
• High solubility of mimetics

Figure 2. Inhibition of p53/hDM2 interaction through helical foldamers. (Rosario, M. 2017)

BOC Sciences’ PPI helix turn 3D-mimetics library includes a diversity of therapeutically relevant compounds that are carefully selected from our proprietary collection of HTS compounds to meet the parameters listed in the table below.

Table1. The summary of the BOC Sciences PPI Helix Turn 3D-Mimetics Library characteristics

Features of PPI Helix Turn 3D-Mimetics Library

• Better diversity
• Complexity
• Access to greater chemical space
• Improved phys-chem parameters (logP; PSA; water solubility etc.)
• Better opportunity to reduce scaffold MW
• Better opportunity for further scaffold modification
• Natural product-likeness
• Better affinity to target proteins
• Greater selectivity
• Easy access to IP-clean field
• All PAIN and reactive compounds are excluded from selection by internal filter applications
• Structurally diverse subset, with the option to favor hit discovery
• Structural analogs available for SAR studies
• All compounds are continually updated
• Compound cherry-picking service is available

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 PPI Helix Turn 3D-Mimetics Library design at competitive prices for global customers. Personalized and customized services of PPI Helix Turn 3D-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!