title: The C-terminal tails of 4,4'-diphenylmethane-bis(methyl) carbamate are essential for binding to receptor for advanced glycation end products to attenuate advanced glycation end products-induced inflammation and apoptosis responses in human umbilical vein endothelial cells.
abstract: OBJECTIVE
  A novel compound 4,4'-diphenylmethane-bis(methyl) carbamate (CM1) was shown to possess preventive activity on AGEs-induced human umbilical vein endothelial cells (HUVECs) damage via binding to RAGE. However, the underlying structural basis of CM1 on binding to RAGE was not fully understood.
  
  
  METHODS
  In the present study, CM1 analogues were designed and synthesized to compare the activity differences on inhibiting AGEs-induced inflammatory response including TGF-β1, RAGE protein expression in HUVECs, and macrophages migration and adhesion to HUVECs. In addition, the cell viability and anti-apoptosis activities of CM1 analogues were also examined.
  
  
  RESULTS
  These results indicated that CM1 had higher activities on preventing AGEs-induced HUVECs damage (inflammation, cell viability and apoptosis) than other analogues. The bioaffinity assay was conducted by CMC and demonstrated that the IC50 and dissociation equilibrium constants (Kd) of CM1 were lower whereas the Bmax was higher than other analogues. The incubation of RAGE protein with CM1 analogues by equilibrium dialysis method showed CM1 had a stronger binding rate than other CM1 analogues.
  
  
  CONCLUSIONS
  Our findings suggested that the C-terminal tails (methoxycarbonyl groups) of CM1 were the active groups for binding to RAGE and then led to the attenuation on RAGE-mediated endothelial dysfunction.
authors.affiliation: Key Laboratory of Delivery Systems of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing, China.|State Key Laboratory of Quality Research in Chinese Medicine, Biotechnology Labortory of Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Feng
authors.affiliation: Key Laboratory of Delivery Systems of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing, China.
authors.forename: Mao-mao
authors.initials: MM
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Delivery Systems of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing, China.|Jiangsu Provincial Combine Traditional Chinese and Western Medicine Hospital, Jiangsu, Nanjing, China.
authors.forename: Wei-quan
authors.initials: WQ
authors.lastname: Bu
authors.affiliation: Key Laboratory of Delivery Systems of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing, China.
authors.forename: Chun-fei
authors.initials: CF
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Biotechnology Labortory of Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, China.
authors.forename: Zhao-guang
authors.initials: ZG
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Biotechnology Labortory of Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, China.|Institute of Conson Co. for Chinese Medicine in Kidiney Diseases and Consun Pharmaceutical Group, Guangzhou, China.
authors.forename: Ru-shang
authors.initials: RS
authors.lastname: Wang
authors.affiliation: Key Laboratory of Delivery Systems of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing, China.
authors.forename: Xiao-bin
authors.initials: XB
authors.lastname: Jia
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Biotechnology Labortory of Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, China.|Institute of Conson Co. for Chinese Medicine in Kidiney Diseases and Consun Pharmaceutical Group, Guangzhou, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002219:Carbamates / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: C572821:4,4'-diphenylmethane-bis(methyl)carbamate; D002219:Carbamates; D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D053773:Transforming Growth Factor beta1
keywords: 4,4'-diphenylmethane-bis(methyl) carbamate; C-terminal tails; Endothelial dysfunction; RAGE