The Chemical Biology Approach

Altogether, these findings demonstrated that PYRl and PYLs are required for mediating multiple ABA responses in vivo and display differential binding affinities for natural and synthetic agonists. 

Y2H screening (also known as a yeast-two-hybrid system) is a chemical biology technique widely used to discover protein-protein interactions of a protein of interest. 

the defective pyrl mutants from the previous PYR screen were tested for an ABA-responsive interaction with HABl. and the PYRl L 

Complex protein mixture incubation with immobiiized antibody  

In summary, at least six proteins from the 14-membered PYR/PYL gene family showed ABA responsiveness in yeast. The observed selectivity within the pyripyl genes toward AB A-triggered formation of protein - protein complexes with H AB1 indicates that the ABA pathway may be dissected using selective PYR/PYL small-molecule agonists. 

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A review of neuropeptide data from PC2 and PCl/3 knockout mice shows that the majority of neuropeptides studies are partially reduced in the knockout compared with wild-type controls. These results indicate roles for PC2 and PCl/3 in neuropeptide production. Importantly, the partial reduction of neuropeptides examined in PC2- and PC 1/3-deficient mice also indicates possible roles for other proteases for processing proneuropeptides, such as cathepsin L in secretory vesicles for neuropeptide production that has been discussed in this article. Thus, the chemical biology approach has identified fhe novel cafhepsin L cysfeine protease pafhway as a candidafe route for neuropeptide production. 

R. J. Pieters, D. T. S. Rijkers, and R. M. J. Liskamp, Application of the 1,3-dipolar cycloaddition reaction in chemical biology Approaches toward multivalent carbohydrates and peptides and peptide-based polymers, QSAR Comb. Sci., 26 (2007) 1181-1190. 

It is worth noting that the radical damage to methionine-containing peptides and proteins consists of a desulfurization process, which leads to the replacement of a methionine residue with an a-aminobutyric acid in the sequence. This could be a posttranslational modification, which is linked to a postsynthetic modification of lipids by the above-reported tandem mechanism. A chemical biology approach can be proposed involving lipidomics and proteomics, in order to configure the metabolic changes related to a radical stress. 

T he modification of the properties of proteins by treatment with chemi-cals is widely used in fundamental studies (I). Since small changes in the chemical structures of proteins can result in large changes in their physical and biological properties, the chemical modification approach has been successfully applied to many biochemical problems. Most of these studies have been designed to obtain information concerning the mechanisms of action of biologically active proteins like enzymes. 

This conceptually simple approach, described more than 10 years ago [3], has proved broadly applicable and has been widely adopted not only in the chemical biology community but also across biological research in general. It has also spawned several related technologies, such as systems for reverse dimerization . This chapter will review the various protein-ligand systems that have been designed, and describe examples of their use, both in research and drug discovery. 

As structure function correlations are a central theme of chemical biology approaches and chemical biologists will define WHAT needs to be synthesized, they need excellent synthetic organic chemists as their partners who are skilled to rapidly synthesize in reasonable quantity what is really required. This includes single small molecules as well as small-molecule libraries. I also refer to the categories DOS and TOS, which have been introduced by S.L. Schreiber [5],... 

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