Study on the binding of chiral drug duloxetine hydrochloride to human serum albumin.
Duloxetine holds a special promise as an antidepressant, and its effect depends on its binding to human serum albumin (HSA). For this reason, the binding mechanism of duloxetine with HSA was investigated. The specific binding site in HSA was identified and binding constants were determined. Duloxetine could compete with dansyl-L-proline (DLP), a site II marker for binding to site II. Binding constants between duloxetine and HSA were 1.75x10(3) L mol(-1) and 3.74x10(3) L mol(-1) at pH 7.4 and pH 8.5, respectively. The interaction process of enantiomers and HSA was susceptible to pH change. It was concluded that specific binding position of duloxetine was located in site II, and the B conformation of HSA possibly excelled the N conformation in identifying and binding to enantiomers.
Liu
Xiangping
X
Department of Analytical Chemistry, China Pharmaceutical University, Nanjing 210009, China.
Du
Yingxiang
Y
D001667:Binding, Competitive; D000068736:Duloxetine Hydrochloride; D019075:Electrophoresis, Capillary; D006801:Humans; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013237:Stereoisomerism; D013876:Thiophenes / Q000737:chemistry* / Q000378:metabolism*; D014443:Tyrosine
D012709:Serum Albumin; D013876:Thiophenes; D014443:Tyrosine; D000068736:Duloxetine Hydrochloride