AutoClickChem: most important progress in click chemistry over years

AutoClickChem
http://autoclick.ucsd.edu
PLos Computational Biology, March 2012, Vol 8, Issue 3, e1002397


This work by Durrant and McCammon comes from the marriage of virtual in silico screening and click chemistry. 


In my opinion, it is the most important / significant progress over the years in the field of click chemistry.  


Firstly, the reaction functional groups are automatically detected and click chemistry is accordingly performed to 
generate a virtual library of compouds. 


Secondly, the the compounds are generated automatically in 3-D and ready for docking into protein crystal structures 
and energetics studies.


Thirdly, this application significantly narrows down the better binders / inhibitors from gigantic theoretical numbers 
to a small workable few or certain top percentage.


Fourthly, those candidates are made by click chemistry with ease and speed in high yields, ready for bench screening.   


The program was examined and evaluated in two cases, acetycholinesterase inhibitor tacrin and Protein Tyrosine 
Phosphatase 1B inhibitors. The results matched experimental well.

The program is freely available and a server-application allows online use without installation.

Click linker length adjustment for enzyme inhibition

Org. Biomol. Chem. 2011, 9, 5373 Selectin of the biological activity of DNJ neoglycoconjugates through click length variation of the side chain


Click chemistry was applied to create neoglycoconjugates from deoxynojirimycin and adamantane,  These were bioassayed against a few enzymes as inhibitors or agonist. 


These molecules featured both very hydrophilic and hydrophobic end groups, joined by triazole groups giving spacers / linkers with different lengths. These allow some specificity in terms of different targeted proteins.