Synthetic apolipoprotein e mimicking polypeptides and...

C - Chemistry – Metallurgy – 07 – K

Patent

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Details

C07K 14/775 (2006.01) C07K 14/435 (2006.01) C07K 14/47 (2006.01)

Patent

CA 2697957

The present invention provides novel synthetic apolipoprotein E (ApoE)-mimicking peptides wherein the receptor binding domain of apolipoprotein E is covalently linked to 18A, the well characterized lipid-associating model class A amphipathic helical peptide, or a modified version thereof. Such peptides enhance low density lipoprotein (LDL) and very low density lipoprotein (VLDL) binding to and degradation by fibroblast or HepG2 cells. Also provided are possible applications of the synthetic peptides in lowering human plasma LDL/VLDL cholesterol levels, thus inhibiting atherosclerosis. The present invention also relates to synthetic peptides that can improve HDL function and/or exert anti-inflammatory properties.

La présente invention concerne, d'une part de nouveaux peptides synthétiques analogues d'apolipoprotéine E avec un domaine de liaison au récepteur de l'apolipoprotéine E lié à 18A par covalence, d'autre part le peptide hélicoïdal amphipathique de classe A au model d'association aux lipides bien caractérisés, ou enfin l'une de leurs versions modifiées. De tels peptides renforcent la liaison des lipoprotéines basse densité (LDL) et des lipoprotéines très basse densité (VLDL) avec le fibroblaste ou les cellules HepG2 et leur dégradation par les mêmes. L'invention concerne également de possibles applications de ces peptides synthétiques pour faire baisser les niveaux de cholestérols LDL/VLDL dans le plasma humain, et donc pour inhiber l'athérosclérose. L'invention concerne enfin des peptides synthétiques capables d'améliorer la fonction HDL et/ou d'avoir des propriétés anti-inflammatoires.

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