Reversible binding of antidiabetic drugs, repaglinide and gliclazide, with human serum albumin.
Mechanism of interaction of antidiabetic drugs, repaglinide and gliclazide, to human serum albumin has been studied using fluorescence spectroscopic technique. Repaglinide had much higher affinity for human serum albumin when compared with gliclazide. The order of association constants was 10(5) for both the drugs. The size, hydrophobicity and flexibility of the drug molecules play a major role in explaining the binding behaviour of these drugs. Hydrophobic interactions are predominantly involved in the binding. However, drugs do not share common sites with 1-anilinonaphthalene-8-sulphonate on the human serum albumin molecule. Both tyrosine and tryptophan residues participate in the interaction. Repaglinide and gliclazide are bound to site II on the human serum albumin molecule, and the aromatic ring of 411Tyr appears to be involved in binding within site II. Although they do not bind at site I, their binding at site II may cause conformational changes thereby affecting the binding of other ligands to site I. Site-specificity can be useful in predicting the competitive displacement of these drugs by other co-administered drugs, resulting in fluctuations of the blood glucose levels in diabetic patients. Stern-Volmer analysis of quenching data indicated that the tryptophan residues are not fully accessible to the drugs and predominantly dynamic quenching mechanism is involved in the binding.
Seedher
Neelam
N
Department of Chemistry, Panjab University, Chandigarh 160014, India.
Kanojia
Mamta
M
D000817:Anilino Naphthalenesulfonates / Q000737:chemistry; D001665:Binding Sites; D002219:Carbamates / Q000737:chemistry / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000737:chemistry; D005907:Gliclazide / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000378:metabolism*; D008954:Models, Biological; D010880:Piperidines / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics; D014364:Tryptophan / Q000737:chemistry
D000817:Anilino Naphthalenesulfonates; D002219:Carbamates; D005456:Fluorescent Dyes; D007004:Hypoglycemic Agents; D010880:Piperidines; D012709:Serum Albumin; C027132:1-anilino-8-naphthalenesulfonate; C072379:repaglinide; D014364:Tryptophan; D005907:Gliclazide