Conventional high-throughput screening methods and algorithms cannot handle complex biological systems in a cost-effective manner. Fragment-based methods have offered fruitful results in finding new targeted protein-protein interaction (PPI) inhibitors. Compared with HTS, fragment-based drug discovery (FBDD) has proven to be a better method for designing new PPI modulators because the PPI interface is usually composed of discontinuous hot-spots. Nuclear magnetic resonance (NMR), X-ray crystallography, surface plasmon resonance (SPR) and mass spectrometry (MS) can be used to discover and verify thep0. PPI is one of the most attractive targets for modern drug design and development. The crystal structure of the proteins involved reveals the mechanism of tight junctions between interfaces. However, there are no universal features for all proteins involved in it. The focused on inhibiting protein-protein interactions can facilitate PPI research. BOC Sciences PPI Library represents a key compound library covering the chemical space of PPI inhibitors. The PPI Library carefully designed by our scientists comprise compounds that are selected based on the recently released PPI inhibitor models and similarity search.
Figure 1. Protein-protein interactions (PPI) identification. (Dario, D. S.; et al. 2018)
Our Methods
- A decision tree algorithm based on multiple molecular shapes and functional group descriptors is used to provide efficient partitioning between PPI inhibitors and non-PPI inhibitors
- Bayesian modeling (ECFP6 and FCFP6 fingerprints): Some physicochemical descriptors (MW, HBD, HBA, LOGP, RB, No. ring) have been considered in each model. Final compound selection is carried out with Bayesian similarity score cut-off. Compounds with reactive groups are removed from the library.
- Libraries are carefully filtered by Lipinski rules, in which compounds with reactive groups and confounding inhibitors are also removed from the library
PPI Fragment Library Characteristics
At BOC Sciences, our PPI Fragment Library contain more than 7,000 readily-available fragment-like compounds for PPI-related FBDD, which is the largest and most reliable source of high-quality fragments. We cooperate with leading experts in the field of FBDD to design and supply top-level fragment libraries, aiming to meet needs of each client.
Table1. The summary of the BOC Sciences PPI Fragment Library characteristics
| Parameter | Value |
| MW | 250 - 450 |
| ClogP | 2.5 - 4.5 |
| Number of Rotatable Bonds | ≤8 |
| Number of H Donors | ≤3 |
| Number of H Acceptors | ≤5 |
| Number of Rings | >0 |
| Compounds with ‘undesirable’ functionalities | Removed |
| Fsp3 | > 0.4 |
| TPSA | <75 Å2 |
| Hydrophobic cores | 1-5 |
| npr1+npr2 | >1.07 |
Features of PPI Fragment Library
- No PAINS, REOS or toxic substances/unwanted functions: filtered by previously reported and internally developed pharmaceutical chemical filters
- We have compiled a series of characteristics to deliver a special chemical space for compounds with a common function of PPI interaction inhibition
- The principal moment of inertia (PMI) is applied to characterize the PPI fragments. Mean values of npr1=0.22 and npr2=0.89 show the distribution of the compound in 3D space and evaluate the diversity of 3D shapes
- Based on our comprehensive analysis of the published data, we have developed a set of descriptors and ranking mechanisms of arraying fragments, allowing us to design a proprietary PPI Fragment Library for PPI-related FBDD
- In order to enhance the selectivity, we propose a hydrophobic and more spatial structure (sp³-enriched)
- Our screening set intersects the fragment and PPI inhibitor chemical space
- Cherry picking is available
- Support various formatting
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
- Analytical data is provided
BOC Sciences provides professional, rapid and high-quality services of PPI Fragment Library design at competitive prices for global customers. Personalized and customized services of PPI Fragment 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!
Reference
- Dario, D. S.; et al. Large Scale Proteomic Data and Network-Based Systems Biology Approaches to Explore the Plant World. Proteomes. 2018, 6(2): 27.
