Peptidomimetic Library

A large number of bioactive peptides have been identified and characterized. These bioactive peptides can affect cell-cell communication, participate in protein-protein interactions (PPI), cell signaling and control a range of important functions. Peptidomimetics are a type of organic molecules that mimic the action of peptides, which are designed to points of concern linked to natural peptides and to improve other characteristics. These molecules are structurally similar to peptides, but differ significantly in terms of their side chains or molecular backbones. Therefore, the design and synthesis of peptide mimics undoubtedly have great potential in drug discovery.

BOC Sciences has developed different synthetic strategies to modulate the conformational flexibility and the peptide properties of peptidomimetic compounds. Synthetic compounds can be used as peptide secondary structure mimics (α-helix, β-turn and β-chain).

Figure 1. Example of a PPI with its interaction area and hot spots. (Pelaygimeno, M.; et al. 2015)

Advantages of Peptidomimetic

• Enhanced receptor affinity and selectivity
• Increased potency
• Good bioavailability

Library Design

BOC Sciences primarily employ ligand-based approaches including various similarity analysis techniques, such as structural similarity searches with known peptidomimetic inhibitors and scaffolds, 3D shape screening, pharmacophore screening and complex substructure searches:

• We can perform a 2D similarity analysis against known peptidomimetic inhibitors and scaffolds with a Tanimoto index ≥ 0.8
• Our groups can conduct a 3D shape screening against over 1 million conformations generated from the BOC Sciences HTS compounds collcection using pharmacophore type volumes. The screening is based on 3D structures of α-helix and β-turn (type I and II), obtained with quantum mechanics calculations
• Pharmacophore screening includes the construction of a pharmacophore model based on 3D structure of β-turn. The models contain specific exclusion volume constraints and donor/acceptor atom positions to allow the formation of hydrogen bonds in β-turn mimetics
• In addition, complex substructure searches involve search queries based on α-helix and β-turn peptidomimetic scaffolds obtained from the literature, such as various bicyclic, spiro, macrocyclic, pyrrolizidine, triplet, oligobenzamide, anthracene and other scaffolds

Figure 2. Turns with general stabilization and mimicking approaches. (Pelaygimeno, M.; et al. 2015)

What we offer

• α-Helix Mimetics Library

We have prepared an α-helical mimetics library using active template compounds from the literature, and developed two models for each training set. The first one is developed based on FCFP6 fingerprints, and the second one is based on ECFP6. A variety of molecular descriptors such as LogP, molecular weight, number of hydrogen donors and acceptors, number of rotatable bonds, number of rings and molecular polar surface area are involved in the construction of the models to improve accuracy

• β-Turn Mimetics Library

BOC Sciences can develop two selection procedures and diversity clustering. The first selection is performed using a pharmacophore screening, in which the pharmacophore model is based on the real β-turn structure. The second selection is performed by employing a similarity search against known scaffolds of β-turn peptidomimetic, such as pentameric and hexameric cyclic scaffolds, bicyclic scaffolds, etc.

Peptidomimetic 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. Helices with corresponding stabilization and mimicking approaches. (Pelaygimeno, M.; et al. 2015)

BOC Sciences’ peptidomimetic 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 Peptidomimetic Library characteristics

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 Peptidomimetic Library design at competitive prices for global customers. Personalized and customized services of Peptidomimetic 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!