Sirtiun 5 (SIRT5) is a NAD
+
-dependent protein
lysine
deacylase primarily located in mitochondria. SIRT5 displays an affinity
for negatively charged acyl groups and mainly catalyzes lysine deglutarylation,
desuccinylation, and demalonylation while possessing weak deacetylase
activity. SIRT5 substrates play crucial roles in metabolism and reactive
oxygen species (ROS) detoxification, and SIRT5 activity is protective
in neuronal and cardiac physiology. Moreover, SIRT5 exhibits a dichotomous
role in cancer, acting as context-dependent tumor promoter or suppressor.
Given its multifaceted activity, SIRT5 is a promising target in the
design of activators or inhibitors that might act as therapeutics
in many pathologies, including cancer, cardiovascular disorders, and
neurodegeneration. To date, few cellular-active peptide-based SIRT5
inhibitors (SIRT5i) have been described, and potent and selective
small-molecule SIRT5i have yet to be discovered. In this perspective,
we provide an outline of SIRT5’s roles in different biological
settings and describe SIRT5 modulators in terms of their mode of action,
pharmacological activity, and structure–activity relationships.
Green Chemistry has become a hot topic on which not only many companies but also researchers have focused their attention. Green Chemistry strives to identify alternative and environmentally friendly reaction...
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