Abstract：
:Lysosomal enzymes are responsible for the degradation of a wide variety of glycolipids, oligosaccharides, proteins, and glycoproteins. Inherited mutations in the genes that encode these proteins can lead to reduced stability of newly synthesized lysosomal enzymes. While often catalytically competent, the mutated enzymes are unable to efficiently pass the quality control mechanisms of the endoplasmic reticulum, resulting in reduced lysosomal trafficking, substrate accumulation, and cellular dysfunction. Pharmacological chaperones (PCs) are small molecules that bind and stabilize mutant lysosomal enzymes, thereby allowing proper cellular translocation. Such compounds have been shown to increase enzyme activity and reduce substrate burden in a number of preclinical models and clinical studies. In this Perspective, we review several of the lysosomal diseases for which PCs have been studied and the SAR of the various classes of molecules.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Boyd RE,Lee G,Rybczynski P,Benjamin ER,Khanna R,Wustman BA,Valenzano KJdoi
10.1021/jm301557ksubject
Has Abstractpub_date
2013-04-11 00:00:00pages
2705-25issue
7eissn
0022-2623issn
1520-4804journal_volume
56pub_type
杂志文章,评审abstract：:Short peptide-based inhibition of fusion remains an attractive goal in antihuman immunodeficiency virus (HIV) research based on its potential for the development of technically and economically desirable antiviral agents. Herein, we report the use of the dithiol bisalkylation reaction to generate a series of m-xylene ...
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abstract：:Selective inhibitors of the two paralogue KAT3 acetyltransferases (CBP and p300) may serve not only as precious chemical tools to investigate the role of these enzymes in physiopathological mechanisms but also as lead structures for the development of further antitumor agents. After the application of a molecular prun...
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doi：10.1021/jm00228a002
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更新日期：1991-01-01 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
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doi：10.1021/jm00152a017
更新日期：1986-02-01 00:00:00
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