An Overview of Drug Binding to Human Serum Albumin: Protein Folding and Unfolding

Human serum albumin (hsa) is a principal extracellular protein with a high concentration inblood plasma and a carrier of many drugs to different molecular targets. drug binding to hsacan alter the protein biophysical and biochemical properties of protein. the structural analysisof human serum albumin complexes, with naturally occurring flavonoids quercetin (antioxidant),kaempferol (antioxidant), delphinidin (antioxidant), azt (3'-azido-3'-deoxythymidine) (antiaids),aspirin (anti-inflammatory), taxol (anticancer), cisplatin (anticancer), atrazine (herbicide),2,4-0 (herbicide), polyamines (biogenic), chlorophyll (antimutagenic), chlorophyllin(antitumor), poly(ethylene glycol) (polymer), vandyl cation and vanadate anion in aqueoussolution are reported. using capillary electrophoresis, ftir (fourier transform infrared), uvvisibleand cd (circular dichroism) spectroscopic methods, the drug binding mode, the bindingconstant and the effects of drug complexation on protein secondary structure are determined.the concentrations of hsa used were 0.6 to 0.3 mm, while different drug concentrations were1 jlm to 1 mm. structural analysis showed drugs are mostly located along the polypeptide chains,with both specific and non-specific interactions. the stability of drug-hsa complexes were in-i> -i>the order: keb == 1.2x 108 mkazt == 1.9 x 106 mkdel == 4.7 x 105m-i> !(peg ==3.5 x 104m-i>4.1 x 105m-i> kkae == 2.6 x 105m-i> k que == 1.4 x 105m-i> katrazine ==104m-1 104m-i 104m-ikchlorophyll == 2.9 x > !{2,4-d == 2.5 x > kspermine == 1.7 x >ktaxol == 1.43 x 104m-i> kaspirin == 1.04 x 104m-i> kchlorophyllin == 7.0 x 103m-i> k v0 3 == 103m-i>6.0 x 103 m-i > kspermidine == 5.4 x 103 m-1 > kputrescine == 3.9 x kcisplatin ==1.2 x 102m-i . at low drug concentration (1 jlm), protein conformation was not altered (infrared and cd results), while, at high drug content (1 mm), a major reduction of a-helix from 6055%(free hsa) to 49-40% and an increase of tj-structure from 22-15% (free hsa) to 33-23% in the drug-protein complexes occurred. these observations indicated that low drug content induced protein stabilization (folding), whereas, at high drug concentration, a partial protein destabilization (unfolding) occurred in these drug-hsa complexes