Sergiy O. Cherenok

Inhibition of Yersinia protein tyrosine phosphatase by phosphonate derivatives of calixarenes.

Inhibition of Yersinia protein tyrosine phosphatase by calix[4]arene mono-, bis-, and tetrakis(methylenebisphosphonic) acids as well as calix[4]arene and thiacalix[4]arene tetrakis(methylphosphonic) acids have been investigated. The kinetic studies revealed that some compounds in this class are potent competitive inhibitors of Yersinia PTP with inhibition constants in the low micromolar range. The binding modes of macrocyclic phosphonate derivatives in the enzyme active center have been explained using computational docking approach. The results obtained indicate that calix[4]arenes are promising scaffolds for the development of inhibitors of Yersinia PTP.

Calix[4]arene methylenebisphosphonic acids as inhibitors of protein tyrosine phosphatase 1B

Сalix[4]arenes bearing methylenebisphosphonic or hydroxymethylenebisphosphonic acid fragments at the wide rim of the macrocycle were studied as inhibitors of PTP1B. Some of the inhibitors showed IC50 values in the micromolar range and good selectivity in comparison with other protein tyrosine phosphatases such as TC-PTP, PTPβ, LAR, and CD45. Kinetic studies indicated that the calix[4]arene derivatives influence PTP1B activity as slow-binding inhibitors. Based on molecular docking results, the binding modes of the macrocyclic bisphosphonates in the active centre of PTP1B are discussed.

HPLC Study of Phosphorylcalixarene Complexation with Organic Substrates

Abstract Host–guest complexation of the calixarenes as well as thiacalixarenes bearing phosphoryl or sulfonate residues at the upper rim with a series of amino acids, uracils, adenines, and nucleotides (ADP and ATP) in water or water–organic solutions was investigated by high-performance liquid chromatography. Association constants of the 1:1 stoichiometry complexes were calculated from a ratio between the capacity factor of the guests and calixarene concentration in the mobile phase.

Bio-Relevant Derivatives of Calixarene Phosphonic Acids

The calix[4]arenes functionalized at the macrocyclic upper rim with α-hydroxyphosphonic, α-aminophosphonic or methylnebisphosphonic acid groups were synthesized. The complexes formed between the bio-relevent calix[4]arene derivatives and amino acids or dipeptides as well as inhibition effects of calix[4]arene phosphonic acids on alkyline phosphatases acitiy were studied.

Complexation of calix[4]arenehydroxymethylphosphonic acids with amino acids. Binding constants determination of the complexes by HPLC method

Host–Guest complexation process of calixarenehydroxymethylphosphonic acids with 10 amino acids in solution H2O/MeCN (99:1) had been studied. Binding constants of the inclusion complexes from the dependence between capacity factors of the Guest and the calixarene-Host concentration in the mobile phase had been calculated. It was shown the binding constants depend on the nature of the amino acid residue, conformation of the calixarene skeleton, quantity of phosphoryl groups at the upper rim. In accordance with molecular calculation the complexation is determined by the electrostatic interactions between the positively charged nitrogen atom of amino acid and the negatively charged oxygen atom of phosphonic group of calixarene molecule, hydrogen bonds, π–π, CH–π and solvatophobic, interactions.

Supramolecular Chemistry of Phosphorus-Containing (Thia)Calixarenes

Molecular modeling, synthesis, and structural investigations of the phosphorus-containing (thia)calixarenes and their supramolecular complexes with biorelevant or ecologically hazardous molecules and ions are discussed within the context of cationic and molecular recognition, extraction properties, and bioactivity.

Phosphorylated Calix[4]arenes as Inhibitors of Glutathione S-Transferase

Abstract Phosphorylated derivatives of calix[4]arene were evaluated as inhibitors of glutathione S-transferase. Computer-simulated docking studies showed that phosphorylated macrocycle is located near the G-site of the enzyme.

Synthesis of Calixarene-Methylenebisphosphonic Acids and Their Influence on Fibrin Polymerization

Abstract A series of hydroxycalix[4]arenes bearing one, two, or four fragments of methylenebisphosphonic acids was synthesized by the reaction of appropriate formylcalixarenes with sodium salts of dialkylphosphites. These calixarenes inhibit specifically 50% of fibrin polymerization in the fibrinogen + thrombin reaction as well as monomeric fibrin desAABB polymerization in concentration up to 0.5 × 10−6 M.

Calixarene Phosphonous Acids: Synthesis and Biological Activity

Abstract The cone shaped сalix[4]arene hydroxyphosponous, ketophosphonous, methylenebisphosphonous, and hydroxymethylenebisphosphonous acids are specific inhibitors of glutathione S-transferase, ATPases of smooth muscle cells, fibrin polymerization processes GRAPHICAL ABSTRACT

A Novel Approach to the Design of Phosphonate Inhibitors of Protein Tyrosine Phosphatase

Inhibition of some PTPases by mono-, bis-, and tetrakisphosphorylated calix[4]arenes have been investigated. Kinetics and computational docking studies provide a basis for understanding the mechanism of enzyme–inhibitor complexation, which may be useful for the development of potent inhibitors of the PTPases.