77113-63-4Relevant academic research and scientific papers
Immobilization of malarial (Plasmodium falciparum) dihydrofolate reductase for the selection of tight-binding inhibitors from combinatorial library
Thongpanchang, Chawanee,Taweechai, Supannee,Kamchonwongpaisan, Sumalee,Yuthavong, Yongyuth,Thebtaranonth, Yodhathai
, p. 5006 - 5012 (2008/02/08)
A simple procedure for selection of tight-binding inhibitors of mutant dihydrofolate reductases from Plasmodium falciparum (PfDHFRs) based on preferential binding to the enzyme immobilized on a Sepharose column has been described. PfDHFRs with a cysteine residue at the C-terminal have been prepared in order to immobilize to a thiopropyl-Sepharose gel via S-S linkage. The amount of immobilized DHFRs was estimated to be 4-5 mg/g of dried gel, and the activities of bound DHFRs were comparable to that of free enzymes. The prepared immobilized enzyme has been used for the selection of tight-binding inhibitors from combinatorial libraries, based on the affinities of each ligand with the enzyme. Free ligands were then identified and analyzed quantitatively by high-performance liquid chromatography-mass spectrometry, and the components with high binding affinity of the library could thus be realized. Results could be confirmed by quantitative analysis of the bound ligands released from the enzyme by guanidine hydrochloride treatment.
Design, synthesis, and evaluation of inhibitors of trypanosomal and leishmanial dihydrofolate reductase
Chowdhury, Shafinaz F.,Villamor, Victor Bernier,Guerrero, Ramon Hurtado,Leal, Isabel,Brun, Reto,Croft, Simon L.,Goodman, Jonathan M.,Maes, Louis,Ruiz-Perez, Luis M.,Pacanowska, Dolores Gonzalez,Gilbert, Ian H.
, p. 4300 - 4312 (2007/10/03)
This paper concerns the design, synthesis, and evaluation of inhibitors of leishmanial and trypanosomal dihydrofolate reductase. Initially study was made of the structures of the leishmanial and human enzyme active sites to see if there were significant d
