Abstract
6-Mercaptopurine (6-MP) is one of a large series of purine analogues which has been found active against human leukemias. The equilibrium dialysis, circular dichroism (CD) and molecular docking were employed to study the binding of 6-MP to human serum albumin (HSA). The binding of 6-MP to HSA in the equilibrium dialysis experiment was detected by measuring the displacement of 6-MP by specific markers for site I on HSA, warfarin (RWF), phenylbutazone (PhB) and n-butyl p-aminobenzoate (ABE). It was shown, according to CD data, that binding of 6-MP to HSA leads to alteration of HSA secondary structure. Based on the findings from displacement experiment and molecular docking simulation it was found that 6-MP was located within binding cavity of subdomain IIA and the space occupied by site markers overlapped with that of 6-MP. Displacement of 6-MP by the RWF or PhB was not up the level expected for a competitive mechanism, therefore displacement of 6-MP was rather by non-cooperative than that the direct competition. Instead, in case of the interaction between ABE and 6-MP, when the little enhancement of the binding of ABE by 6-MP was found, the interaction could be via a positively cooperative mechanism.
Highlights
6-Mercaptopurine (6-MP) is one of a large series of purine analogues which has been found active against human leukemias
The equilibrium dialysis, circular dichroism (CD) and molecular docking were employed to study the binding of 6-MP to human serum albumin (HSA)
The alone Trp214 residue is located in the hydrophobic pocket in the binding subdomain IIA within the non-overlaping part of the warfarin region in which plays an important role in binding process of warfarin and acenocoumarol, whereas is not related to azapropazone binding region where phenylbutazone and other non-steroid anti-inflammatory drugs bind
Summary
6-Mercaptopurine (6-MP) is one of a large series of purine analogues which has been found active against human leukemias. The binding of 6-MP to HSA in the equilibrium dialysis experiment was detected by measuring the displacement of 6-MP by specific markers for site I on HSA, warfarin (RWF), phenylbutazone (PhB) and n-butyl p-aminobenzoate (ABE). It was shown, according to CD data, that binding of 6-MP to HSA leads to alteration of HSA secondary structure. Abbreviations ABE n-Butyl p-aminobenzoate CD Circular dichroism HSA Human serum albumin 6-MP 6-Mercaptopurine MVD Molegro Virtual Docker PDB World wide web Protein Data Bank PhB Phenylbutazone RWF Warfarin. The alone Trp214 residue is located in the hydrophobic pocket in the binding subdomain IIA within the non-overlaping part of the warfarin region in which plays an important role in binding process of warfarin and acenocoumarol, whereas is not related to azapropazone binding region where phenylbutazone and other non-steroid anti-inflammatory drugs bind
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