Synthesis and testing of trifluoromethyl-containing phosphonate-peptide conjugates as inhibitors of serine hydrolases

Nadezhda V Sokolova; Valentine G Nenajdenko; Vladimir B Sokolov; Olga G Serebryakova; Galina F Makhaeva

doi:10.1016/j.bmcl.2011.09.030

Synthesis and testing of trifluoromethyl-containing phosphonate-peptide conjugates as inhibitors of serine hydrolases

Bioorg Med Chem Lett. 2011 Dec 1;21(23):7216-8. doi: 10.1016/j.bmcl.2011.09.030. Epub 2011 Sep 16.

Authors

Nadezhda V Sokolova¹, Valentine G Nenajdenko, Vladimir B Sokolov, Olga G Serebryakova, Galina F Makhaeva

Affiliation

¹ Department of Chemistry, Moscow State University, Moscow, Russia.

PMID: 22001085
DOI: 10.1016/j.bmcl.2011.09.030

Abstract

A modification of novel fluorinated organophosphorous compounds containing terminal alkyne group by different azidopeptides via Cu(I)-catalyzed click chemistry has been described. The inhibitor activity of trifluoromethyl-containing methylphosphonates and their peptide-conjugates towards acetylcholinesterase, butyrylcholinesterase, and carboxylesterase has been investigated. It was shown that the incorporation of peptide fragments significantly modulates the esterase profile of starting methylphosphonates.

MeSH terms

Carboxylesterase / antagonists & inhibitors
Catalysis
Cholinesterase Inhibitors / chemical synthesis
Cholinesterase Inhibitors / chemistry
Cholinesterase Inhibitors / pharmacology
Click Chemistry
Enzyme Activation / drug effects
Fluorine / chemistry
Inhibitory Concentration 50
Molecular Structure
Organophosphonates / chemical synthesis*
Organophosphonates / chemistry
Organophosphonates / pharmacology
Peptides / chemical synthesis*
Peptides / chemistry
Peptides / pharmacology
Serine Proteinase Inhibitors / chemical synthesis*
Serine Proteinase Inhibitors / pharmacology

Substances

Cholinesterase Inhibitors
Organophosphonates
Peptides
Serine Proteinase Inhibitors
Fluorine
Carboxylesterase