Drug click chemistry

Sharpless, K. B. Manetsch, R. In situ click chemistry A powerful means for lead discovery. Expert Opin. Drug Discov. 2006,1, 525-538. 

Inhibition can be reversible when it simply complexes at the active site preventing further catalysis. The active enzyme under these conditions can be recovered by dialysis. Another form of inhibition is the irreversible type where the active enzyme cannot be recovered by dialysis. A variant of this type of inhibition is suicide inhibition a substrate of the enzyme reacts at the active site to yield an irreversible inhibitor which then reacts directly with groups at the active site [18]. A technique, in situ click chemistry , is related to that of suicide inhibition and involves click chemistry components which complex at the active site of an enzyme and combine to form femtomolar inhibitors. The technique can be used to synthesise inhibitors or by selection from a library of click chemistry components to search structure space of the inhibitor for the drug target [ 19]. 

Like DCC, applying in situ Click chemistry against drug discovery targets necessitates the identification of the best binding ligands. The experimental reaction mixture for in situ Click chemistry shares many component attributes in common with DCC, namely... 

Kolb, H. C. and Sharpless, K. B. (2003). The growing impact of click chemistry on drug discovery. Drug Discov. Today 8, 1128-1137. 

As a basis for hydrogels, hyperbranched polymers [41] can also be used. These polymers can be connected by click chemistry in miniemulsion droplets in order to obtain hyperbranched polyglycerol (HPG)-based particles. Such materials are of great interest for drug release because they are nontoxic [42, 43] and show similar behavior to poly(ethylene glycol)s. 

Due to the reliability, specificity and biocompatibility of click chemistry, its application is found in nearly all areas of modern chemistry from drug discovery to material science. 

New techniques used currently for drug design could be used. Among them, molecular docking studies, prediction of new structures using chemometric tools, click chemistry, or random chemistry approaches could be applied to reach the target. 

The simplicity and efficiency of the click chemistry is attractive to fluorine-18 chemistry, where time plays an important role in synthesis due to the relative short half-life of fluorine-18. This one-pot reaction provides a versatile tool for coupling drug-like fragments in high yield and under mild conditions. The product 1,2,3-triazole formed from cycloaddition is biologically stable with polarity and size similar to an amide group that is a common functional group in many radiopharmaceuticals [77],... 

Lutz JF, Zarafshani Z (2008) Efficient construction of therapeutics, bioconjugates, biomaterials and bioactive surfaces using azide-alkyne click chemistry. Adv Drug Deliv Rev 60 958-970... 

Chiral 1,1-diaryl compounds as important pharmacophores 13MCC893. Click chemistry in peptide-based drug design 13MOL9797. N-Containing Ag(I) and Hg(II) complexes as a new class of antibiotics 13CTM3026. 

As another example, poly(glycolide)s have been described that include a polymeric alkynyl-substituted glycoUde (56). The alk-ynyl groups provide reactive sites for further functionalization of the polymer, for example by reaction with azide derivatives. The alkynyl and azide groups react via the click chemistry mechanism to form functional groups covalently bonded to the polymer via a triazole link. The polymers are biodegradable and can be used to deliver drugs or other therapeutic substances at controlled release rates. 

---