Chemoproteomic Analysis of Non-Covalent Drugs

Chemical small molecule drugs occupy a significant position in the field of disease drug research and development. Up to now, among the 812 human protein targets for FDA-approved drugs, 84% correspond to chemical small molecule drugs. For 639 of these targets, only small molecule drugs have been developed. The interaction between chemical small molecule drugs and target proteins can be divided into non-covalent and covalent types. Currently, non-covalent interactions are the predominant form.

 

Technical Principles

If the interaction between active small molecules and target proteins is non-covalent (such as hydrogen bonding and stacking) when they play biological functions, they can be transformed into chemical probes with similar activities. Then, using the in-situ rapid photocrosslinking strategy, non covalent interactions are transformed into covalent interactions in the original biologically active environment, directly capturing the target of active molecules from the proteome, providing more detailed information for revealing the mechanism of action of active small molecules. The method is suitable for various sample systems such as living cells, tissues, cell lysates, etc. The active small molecules include but are not limited to endogenous metabolites, natural products, non-covalent drugs, etc.

 

Workflow

1.Deriving active molecules into photo crosslinked probes

 

2.Light-induced covalent linking proteins

 

3.Protein enrichment

 

4.Protein digestion

 

5.Multiple quantitative labeling

 

6.Mass spectrometry detection

 

7.Analysis of small molecule targets

 

Service at ChemPro Innovations

1.Design and modification of non-covalent drug molecular probes.

 

2.Omics analysis of non-covalent drug targets in molecular proteins based on gel imaging and biomacromolecule mass spectrometry.

 

3.Mass-spec based non-covalent drug binding site analysis.

 

4.Non-covalent drug target verification ( target quantitative protein analysis / western blot).