专利检索 ap:("The U.S.A., as represented by the Secretary, Department of Health AND Human Services") AND inv:"PamelaSara Elbaz Head" 第 1 页

1.

发明公开
ABERRANT POST-TRANSLATIONAL MODIFICATIONS (PTMS) IN METHYL- AND PROPIONIC ACIDEMIA AND A MUTANT SIRTUIN (SIRT) TO METABOLIZE PTMS 审中-公开

公开(公告)号：US20230181672A1

公开(公告)日：2023-06-15

申请号：US17923394

申请日：2021-04-20

申请人： The U.S.A., as represented by the Secretary, Department of Health and Human Services

发明人： Charles P. Venditti , PamelaSara Elbaz Head

IPC分类号： A61K38/00 , C07K14/765

CPC分类号： A61K38/00 , C07K14/765 , C07K2319/43 , C12N2750/14143

摘要： This application provides the first observation of methylmalonylation/malonylation in organic acidemias (OAs), such as methylmalonic acidemia (MMA) and propionic acidemia (PA), which results in modification of enzymes in key pathways dysregulated in OAs, including sirtuin 5 (SIRT5). Hyperacylation of SIRT5 prevents it from de-acylating CPS1 (including removing methymalonyllation), which prevents activation of CPS1 and likewise, inhibits a key component of the glycine cleavage system, GCSH. Based on these observations, provided herein is a mutant form of SIRT5 containing four mutated lysines that cannot accept acyl groups, methods of its use for treating OA patients, and kits.