Interaction studies between human alpha-tocopherol transfer protein and nitric oxide donor tocopherol analogues with LDL-protective activity.
Nitric oxide-releasing alpha-tocopherol mimetics with LDL-protective activity were designed to maintain the tocopherol substructure necessary for its biochemical recognition by alpha-tocopherol transfer protein. In order to study the molecular interactions to alpha-TTP, theoretical binding studies by means of docking techniques and experimental binding assays, using a fluorescent probe, were performed. Furoxanyl-tocopherol-hybrid analogs 7 and 9 have the best ability to bind to alpha-TTP suggesting that they could be incorporated to LDL in vivo to further release nitric oxide and prevent oxidative modifications.
López
Gloria V
GV
Departamento de Química Orgánica, Facultad de Química-Facultad de Ciencias, Universidad de la República, Iguá 4225, 11400 Montevideo, Uruguay. vlopez@fq.edu.uy
Gómez
Luis E
LE
Campillo
Nuria
N
Páez
Juan A
JA
Giles
Kaleigh
K
Atkinson
Jeffrey
J
González
Mercedes
M
Rubbo
Homero
H
Cerecetto
Hugo
H
D019943:Amino Acid Substitution; D000975:Antioxidants / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D024505:Tocopherols / Q000378:metabolism*; D014810:Vitamin E / Q000378:metabolism*; D024502:alpha-Tocopherol
D000975:Antioxidants; D008078:Cholesterol, LDL; D020030:Nitric Oxide Donors; D014810:Vitamin E; D009569:Nitric Oxide; D024502:alpha-Tocopherol; D024505:Tocopherols