Streptozocin; a GLUT2 binding drug, interacts with human serum albumin at loci h6 DOM3 -h7 DOM3

• Published in: International journal of biological macromolecules 2019-05, Vol.128, p.923
• Main Authors: Deshpande, Amogh S, Ramireddy, Sriroopreddy, Sudandiradoss, C, Noor, Ayesha, Sen, Priyankar
• Format: Article
• Language: English
• Subjects: Binding Sites; Entropy; Glucose Transporter Type 2 - metabolism; Humans; Hydrogen-Ion Concentration; Protein Binding; Serum Albumin, Human - chemistry; Serum Albumin, Human - metabolism; Streptozocin - metabolism
• ISSN: 1879-0003
• DOI: 10.1016/j.ijbiomac.2019.01.217

Streptozocin (STZ) is a broad range antibiotic, highly genotoxic, antineoplastic and hyperglycemic. HSA is the most abundant protein in physiology and it binds to almost all exogenic and endogenic ligands, including drugs. STZ-induced fluorescence quenching of HSA has been done at pH 7.4, pH 3.5 and at pH 7.4 with 4.5 M urea at temperatures 286 K, 291 K, and 306 K. K found to be 10  M , binding constant 1.5X10 M and binding sites ~1. But, K for HSA and glucopyranose interaction was found lesser than that of HSA-STZ binding. Binding of STZ/glucopyranose on HSA seems to result in complex formation as calculated K  > 10  M  s . The number of binding sites, binding constants, and binding energies were increased with temperature. The ΔG , ΔH , and ΔS for HSA-STZ interaction were found to be -17.7 × 10  J·mol ; 2.34 × 10  J·mol and 841 JK  mol respectively at pH 7.4 and 291 K. The comparative bindings of N, F and I states of HSA with STZ and their molecular docking analyses indicate that IIIA-B junction (i.e., inter-helix h6 -h7 ) is the probable binding site, a locus close to fatty acid binding site-5. These results could be useful for therapeutic and analytical exploitation of STZ, as albumin used as the vehicle for drug delivery.