NJ Bio is furthermore preparing a library of linkers for the construction of a wide variety of Protein Degrader molecules for screening purposes. The objective of this library is to find an SAR or optimal length of a linker based on targets.
Conjugatable Protein Degraders are available with both cleavable and non-cleavable linkers with similar release mechanisms as for most toxins for ADCs. The advantage of these Protein Degraders is that they are only active when they are intracellular with minimal by-stander effect.
What NJ Bio offers to assist your Protein Degrader research
- Synthesis of Protein Degraders
- Access to a wide range of linkers of varying lengths, attachment points, and chemical compositions.
- Utilization of established ligands to VHL and Cereblon, plus ligands for E3 enzymes that may show superior therapeutic profiles (e.g., MDM2).
- Assays of Protein Degrader activity, in vitro and in cells.
- Discovery of ligands for target proteins via NMR screening, either by using client’s library, selection of a targeted library, or generation of a “maximally diverse” fragment library.
- NMR structural studies of interactions between Protein Degraders and their target proteins, and between components of the target-Protein Degrader-E3 ternary complex.
- Conjugation to protein, antibody and other.
NMR structural studies to aid optimization of Protein Degraders
HSQC experiment using a 15N or 13C labeled component allows rapid, selective monitoring of chemical shift changes upon complex formation. These chemical shift changes typically indicate regions of contact.
|Sample, where [L] designates label||What can be learned|
|Target [L] + Protein Degrader||where on Target does Protein Degrader interact?|
|Target + Protein Degrader [L]||what parts of Protein Degrader contact target?|
|Protein Degrader [L] + E3||what parts of Protein Degrader contact E3?|
|Target + Protein Degrader[L] + E3 (with NOEs)||what is conformation of Protein Degrader in the 3o complex?|
|Target [L] + Protein Degrader + E3||where on Target does E3 interact?|
|Target + Protein Degrader + E3[L]||where on E3 does Target interact?|