Abstract
Abstract: Sirtuin 6 (SIRT6) is an NAD+-dependent deacetylase regulating important functions: modulators of its enzymatic activity have been considered as possible therapeutic agents. Besides the deacetylase activity, SIRT6 also has NAD+-dependent deacylase activity, whereby it regulates the secretion of cytokines and proteins. We identified novel SIRT6 modulators with a lysine-based structure: compound 1 enhances SIRT6 deacylase while inhibiting the deacetylase activity. As expected based on the biological effects of SIRT6 deacetylase activity, compound 1 increased histone 3 lysine 9 acetylation and the activity of glycolytic enzymes. Moreover, the fact that compound 1 enhanced SIRT6 deacylase activity was accompanied by an increased TNF-α release. In conclusion, new SIRT6 modulators with a lysine-like structure were identified, with differential effects on specific SIRT6 activities. Graphic abstract: The novel SIRT6 modulator concomitantly inhibits deacetylase and enhances deacylase activity.[Figure not available: see fulltext.].
| Original language | English |
|---|---|
| Journal | Molecular Diversity |
| DOIs | |
| Publication status | Published - Jan 1 2019 |
Fingerprint
Keywords
- Molecular design
- Sirtuins
- Small molecule SIRT6 modulators
ASJC Scopus subject areas
- Catalysis
- Information Systems
- Molecular Biology
- Drug Discovery
- Physical and Theoretical Chemistry
- Organic Chemistry
- Inorganic Chemistry
Cite this
Differential modulation of SIRT6 deacetylase and deacylase activities by lysine-based small molecules. / Sociali, Giovanna; Liessi, Nara; Grozio, Alessia; Caffa, Irene; Parenti, Marco Daniele; Ravera, Silvia; Tasso, Bruno; Benzi, Andrea; Nencioni, Alessio; Del Rio, Alberto; Robina, Inmaculada; Millo, Enrico; Bruzzone, Santina.
In: Molecular Diversity, 01.01.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Differential modulation of SIRT6 deacetylase and deacylase activities by lysine-based small molecules
AU - Sociali, Giovanna
AU - Liessi, Nara
AU - Grozio, Alessia
AU - Caffa, Irene
AU - Parenti, Marco Daniele
AU - Ravera, Silvia
AU - Tasso, Bruno
AU - Benzi, Andrea
AU - Nencioni, Alessio
AU - Del Rio, Alberto
AU - Robina, Inmaculada
AU - Millo, Enrico
AU - Bruzzone, Santina
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Abstract: Sirtuin 6 (SIRT6) is an NAD+-dependent deacetylase regulating important functions: modulators of its enzymatic activity have been considered as possible therapeutic agents. Besides the deacetylase activity, SIRT6 also has NAD+-dependent deacylase activity, whereby it regulates the secretion of cytokines and proteins. We identified novel SIRT6 modulators with a lysine-based structure: compound 1 enhances SIRT6 deacylase while inhibiting the deacetylase activity. As expected based on the biological effects of SIRT6 deacetylase activity, compound 1 increased histone 3 lysine 9 acetylation and the activity of glycolytic enzymes. Moreover, the fact that compound 1 enhanced SIRT6 deacylase activity was accompanied by an increased TNF-α release. In conclusion, new SIRT6 modulators with a lysine-like structure were identified, with differential effects on specific SIRT6 activities. Graphic abstract: The novel SIRT6 modulator concomitantly inhibits deacetylase and enhances deacylase activity.[Figure not available: see fulltext.].
AB - Abstract: Sirtuin 6 (SIRT6) is an NAD+-dependent deacetylase regulating important functions: modulators of its enzymatic activity have been considered as possible therapeutic agents. Besides the deacetylase activity, SIRT6 also has NAD+-dependent deacylase activity, whereby it regulates the secretion of cytokines and proteins. We identified novel SIRT6 modulators with a lysine-based structure: compound 1 enhances SIRT6 deacylase while inhibiting the deacetylase activity. As expected based on the biological effects of SIRT6 deacetylase activity, compound 1 increased histone 3 lysine 9 acetylation and the activity of glycolytic enzymes. Moreover, the fact that compound 1 enhanced SIRT6 deacylase activity was accompanied by an increased TNF-α release. In conclusion, new SIRT6 modulators with a lysine-like structure were identified, with differential effects on specific SIRT6 activities. Graphic abstract: The novel SIRT6 modulator concomitantly inhibits deacetylase and enhances deacylase activity.[Figure not available: see fulltext.].
KW - Molecular design
KW - Sirtuins
KW - Small molecule SIRT6 modulators
UR - http://www.scopus.com/inward/record.url?scp=85068113933&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85068113933&partnerID=8YFLogxK
U2 - 10.1007/s11030-019-09971-2
DO - 10.1007/s11030-019-09971-2
M3 - Article
JO - Molecular Diversity
JF - Molecular Diversity
SN - 1381-1991
ER -