C - Chemistry – Metallurgy – 07 – H
Patent
C - Chemistry, Metallurgy
07
H
C07H 19/207 (2006.01) A61K 31/70 (2006.01) A61P 35/00 (2006.01) C07H 19/04 (2006.01) C07H 19/10 (2006.01) C07H 19/20 (2006.01) C07K 16/18 (2006.01) C12N 9/99 (2006.01) C12P 19/32 (2006.01)
Patent
CA 2467854
A novel compound, 2'/3'-O-acetyl-ADP-ribose, is provided. The compound is a mixture of the 2' and 3' regioisomers of 0-acetyl-ADP ribose, and is formed nonenzymatically from 2'-O-acetyl-ADP-ribose, which is the newly discovered product of the reaction of Sir2 enzymes with acetylated peptides and NAD+. Analogs of 2'/3'-O-acetyl-ADP-ribose are also provided. Additionally, methods of preparing 2'/3'-O-acetyl-ADP-ribose, methods of determining whether a test compound is an inhibitor of a Sir2 enzyme, methods of detecting Sir2 activity in a composition, methods of deacetylating an acetylated peptide, and methods of inhibiting the deacetylation of an acetylated peptide are provided. Prodrugs of 2'/3'-O-acetyl-ADP-ribose are also provided.
L'invention concerne un composé 2'/3'-O-aceéyl-ADP-ribose. Ce composé est un mélange des isomères de position 2' et 3' d'0-acétyl-ADP ribose, et il et formé par voie non enzymatique à partir de 2'-O-acétyl-ADP-ribose, produit de la réaction d'enzymes Sir2 avec des peptides acétylés et NAD?+¿. L'invention concerne aussi des analogues de 2'/3'-O-acétyl-ADP-ribose. Elle concerne, en outre, des procédés de préparation de 2'/3'-O-acétyl-ADP-ribose, des procédés permettant de déterminer si un composé test est un inhibiteur d'enzyme Sir2, de procédés de détection d'activité Sir2 dans une composition, des procédés de désacétylation et d'acétylation d'un peptide, et des procédés empêchant la désacétylation d'un peptide acétylé. Elle concerne enfin des promédicaments de 2'/3'-O-acétyl-ADP-ribose.
Boeke Jef D.
Celic Ivana
Sauve Anthony
Schramm Vern L.
Albert Einstein College Of Medicine Of Yeshiva University
Osler Hoskin & Harcourt Llp
The Johns Hopkins University
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