Protein Mimetics Library
Selected molecules able to mimic common protein motifs
8 960 compounds
Over 250 000 individual protein-protein interactions (PPIs) were identified in human proteome. Although many of these exhibit topologically complex and formidable surface areas, in many instances the successful binding is attained via a limited number of key residues ("hot spots“). There are multiple reports in the literature describing both computational and diversity-oriented approaches to developing small-molecule modulators of PPIs. Of these, non-peptidic a-helix and b-turn imetics are of particular importance due to their key role in multiple deregulated pathways leading to cancer, neurodegenerative disorders, inflammation and immunological disorders.
Typical Formats
Catalog No.
PML-8960-Y-0
Compounds
8 960 28 plates
Amount
≤ 300 nL of 2 mM solutions in DMSO
Plates and formats
384-well micro plates, Greiner Cat. No. 784201; 1, 2 & 23, 24 columns empty, 320 compounds per plate
Price
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Catalog No.
PML-8960-Y-10
Compounds
8 960 28 plates
Amount
10 µL of 10 mM DMSO stock solutions
Plates and formats
384-well microplates, Echo Qualified, first two and last two columns empty, 320 compounds per plate
Price
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Catalog No.
PML-8960-X-50
Compounds
8 960 112 plates
Amount
50 µL of 10 mM DMSO solutions
Plates and formats
96-well microplates, first and last columns empty, 80 compounds per plate
Price
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Catalog No.
PML-8960
Compounds
8 960
Amount
Custom
Plates and formats
Any custom format
Price
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Library Design
Traditional three residue approach
Alpha-helix Mimetics
Beta-turn Mimetics
Ligand-based approach
Target based approach. We carried out design of a focused compound set targeting selected alpha-helix domains and beta-turns such as mdm2-p53, mdm2-CK1α, HIF1-α , MEF2-HDAC4, HIV-1 gp41, CD81/CV, Bcl-2/Bcl-xL, etc. After the selection by virtual screening the preference was set to the structures bearing new chemotypes.
‘Traditional’ three-residue appraoch included design of compounds with unusual cores bearing regular key-residues that mimics i, i+3/i+4 and i+7-residues located on the one recognition face (‘hot spots’). In modeling a-helix interfaces, we accounted also two-face helix mimetics. For beta-turn mimetics we applied three query models with distinct types of interaction: π-π stacking, cation-π and H-bond interaction, S-π interaction. : The latter focused design exercise was exemplified by modeling the interaction between Bim BH3 domain with Mcl-1 and Bcl-2 and identifying fused polyhydrogenated aza-heterocycles with high Fsp3 character.
Ligand based approach. New chemotypes with close topology to known alpha-helix and beta-turns mimetics were selected. Shape based similarity and Pharmacophore screening were used as a main tools for the library design.
Unique Fsp3-enriched scaffolds exhibiting ladder-like cyclic skeletons were specially selected to enhance topological and pharmacophore interaction with the target alpha-helix and beta-turn motifs.
Examples of Selected Scaffolds in the Library
Molecular properties
