Synthesis of a targeting drug for antifibrosis of liver; a conjugate for delivering glycyrrhetin to hepatic stellate cells.
The neoglycoproteins that consist of human serum albumin (HSA) modified with mannose 6-phosphate ([M6P]x-HSA) were synthesized, and they showed high binding property to hepatic stellate cells (HSC) by immunohistochemical analysis. In addition, an increased substitution (X) of 6-phosphated mannose (M6P) was associated with an increased accumulation in HSC. So the [M6P]x-HSA might be a carrier to deliver drugs to HSC. The antifibrotic drug, glycyrrhetin, was chosen to conjugate to M6P(26)-HSA. The result suggests there were 6 approximately 7 glycyrrhetin molecules having been conjugated to the carrier. Targeting glycyrrhetin to HSC might reduce its adverse affects and increase the efficacy.
Zhang
Jian
J
State Key Laboratory of Bio-Organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, People's Republic of China.
Zhang
Qi-Sheng
QS
Chen
Xiao-Ming
XM
Tian
Geng-Yuan
GY
D002851:Chromatography, High Pressure Liquid; D016503:Drug Delivery Systems / Q000379:methods*; D006023:Glycoproteins / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D006034:Glycyrrhetinic Acid / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use*; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000473:pathology; D008360:Mannosephosphates / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D015394:Molecular Structure; D012709:Serum Albumin / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism
D006023:Glycoproteins; D008360:Mannosephosphates; D012709:Serum Albumin; C027693:mannose-6-phosphate; D006034:Glycyrrhetinic Acid