The interaction of human serum albumin with a novel antidiabetic agent--SU-118.
SU-118 is a newly synthesized antidiabetic agent and shows the best hypoglycemic effect among a series of analogs. Its binding properties and binding sites located on human serum albumin (HSA) have been studied using UV absorption and fluorescence spectroscopy. The results of spectroscopic study and the thermodynamic parameters obtained suggest that SU-118 binds to the hydrophobic cavity of human serum albumin and the hydrophobic interaction is the predominant intermolecular force stabilizing the complex. Fluorescent probe displacement studies show that SU-118 can displace competitively both dansylamide and dansylsarcosine from HSA. It is suggested that SU-118 can bind to both site I and site II, but the primary interaction may take place at site I. A binding constant of 1.4 x 10(4) M(-1) and a binding site of 2.0 are obtained from absorbance titration data. The value of binding constant is of the same order of magnitude as that from fluorescence titration. This study provides a molecular basis for elucidating the mechanism of drug acting and predicting unfavorable drug interaction.
Zhong
Wenying
W
State Key Laboratory of Coordination Chemistry, Nanjing University, Nanjing 210093, People's Republic of China.
Wang
Yuchun
Y
Yu
Jun-Sheng
JS
Liang
Yingqiu
Y
Ni
Kunyi
K
Tu
Shuzi
S
D001665:Binding Sites; D003374:Coumarins / Q000737:chemistry*; D003619:Dansyl Compounds / Q000737:chemistry; D019620:Desulfurococcaceae; D005456:Fluorescent Dyes; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry*; D008856:Microscopy, Fluorescence; D011485:Protein Binding; D012521:Sarcosine / Q000031:analogs & derivatives* / Q000737:chemistry; D012709:Serum Albumin / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D013453:Sulfonylurea Compounds / Q000737:chemistry*; D013816:Thermodynamics; D014364:Tryptophan / Q000032:analysis
D003374:Coumarins; D003619:Dansyl Compounds; D005456:Fluorescent Dyes; D007004:Hypoglycemic Agents; C492958:SU-118; D012709:Serum Albumin; D013453:Sulfonylurea Compounds; C037087:dansylsarcosine; C001026:5-dimethylaminonaphthalene-1-sulfonamide; D014364:Tryptophan; D012521:Sarcosine