Fully Functionalized Probe Library
Phenotypic screening provides a useful tool to identify small molecules that perturb biological processes. However, small molecules often interact with multiple protein targets with weak affinity, and few techniques can accurately and rapidly characterize these interactions, making it difficult to understand the mechanism of pharmacological activity. The concept of phenotypic screening with probes of fully functionalized small molecules has recently been introduced. This approach significantly increases the efficiency and success of target identification after the screening campaign. Fully functional probes are designed to accelerate and simplify the early stages of drug development. The introduction of the diazine-like photocrosslinking moiety and the presence of a functional acetylene group in the probe allows direct screening of compounds in cells.
BOC Sciences has created a Fully Functionalized Probe Library for easy and efficient exploration of novel protein targets.
Application of Fully Functionalized Probe Library
- Integrated phenotypic screening
- Target identification
- Mechanistic characterization
Figure 1. Schematic workflow for evaluating Fully Functionalized tags in human cells through both gel-based fluorescence and MS-based proteomicss. (Conway, L. P.; et al. 2021)
Library Design
We have improved parallel chemistry protocols to synthesize photoaffinity labeled compounds, enabling our customers to quickly access subsequent libraries based on initial screening results. Here are our library design strategies:
- We employ the Ugi-azide multicomponent condensation reaction to develop an efficient synthetic strategy to generate generate structurally diverse libraries
- The diazine group is applied to forge the covalent bond between the probe and the protein target, aiming to minimize the steric footprint of the photocrosslinking element
- A fully functionalized library is designed based on the experimentally confirmed solubility of the fragments in aqueous PBS at a concentration of 1 mM
Fully Functionalized Probe Library Characteristics
At BOC Sciences, the well-established library consist of more than 650 compounds 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 Fully Functionalized Probe Library characteristics
| Parameter | Value |
| MW | 247-404 |
| ClogP | -2.5-4.1 |
| Number of Rotatable Bonds | 5-9 |
| Number of H Donors | ≤3 |
| Number of H Acceptors | 4-9 |
| Number of Rings | >0 |
| Compounds with ‘undesirable’ functionalities | Removed |
| Fsp3 | 0-1 |
| TPSA | <125 Å2 |
| Number of Aromatic Rrings | 0-3 |
| Number of Heavy Atoms | 18-30 |
Features of Fully Functionalized Probe Library
- No PAINS, REOS or toxic substances/unwanted functions: filtered by previously reported and internally developed pharmaceutical chemical filters
- One or more elements of diversity to facilitate interactions with different protein targets in the cell
- Photoreactive groups for UV light-induced covalent cross-linking to interacting proteins
- Alkyne handles for reporter tag conjugation to visualize and identify cross-linked proteins
- Allow for Identification of binding sites for POIs
- Support the direct screening in cells
- Hits can be easily confirmed by LC-MS
- Cover as much structural diversity as possible in order to have different chemotypes and pharmacophores in a limited number of compounds
- Cherry picking service is available
Figure 2. Mapping the Protein Interaction Landscape for Fully Functionalized Small-Molecule Probes. (Kambe, T.; et al. 2014)
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 Fully Functionalized Probe Library design at competitive prices for global customers. Personalized and customized services of Fully Functionalized Probe 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
- Conway, L. P.; et al. Evaluation of fully-functionalized diazirine tags for chemical proteomic applications. Chemical Science. 2021. 12: 7839-7847.
- Kambe, T.; et al. Mapping the protein interaction landscape for fully functionalized small-molecule probes in human cells. Journal of the American Chemical Society. 2014. 136(30): 10777-82.
