Selectivity hot-spots of sirtuin catalytic cores

Marco Daniele Parenti, Santina Bruzzone, Alessio Nencioni, Alberto Del Rio

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Sirtuins are NAD+-dependent deacetylases with several biological roles in DNA regulation, genomic stability, metabolism, longevity and immune cell functions. Numerous disease conditions are linked to sirtuins including metabolic disorders, inflammatory and autoimmune processes and cancer. Although few specific small molecule modulators have been reported to date, the need to identify selective ligands would be crucial not only for the development of active pharmaceutical ingredients for new targeted therapies but also as a tool for dissecting the biological roles of sirtuin family members. Herein, we report a comprehensive study aimed to classify and identify the selectivity hot-spots for targeting the catalytic cores of human sirtuins using small molecule modulators. Our selectivity analysis suggests that catalytic cores can be divided into different clusters that can constitute the basis for the development of selective ligands. The ensemble of hot-spot information is expected to be helpful to devise new selective chemicals targeting sirtuin family members.

Original languageEnglish
Pages (from-to)2263-2272
Number of pages10
JournalMolecular BioSystems
Volume11
Issue number8
DOIs
Publication statusPublished - May 26 2015

Fingerprint

Sirtuins
Catalytic Domain
Ligands
Genomic Instability
NAD
DNA
Pharmaceutical Preparations
Neoplasms
Therapeutics

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Biology

Cite this

Selectivity hot-spots of sirtuin catalytic cores. / Parenti, Marco Daniele; Bruzzone, Santina; Nencioni, Alessio; Del Rio, Alberto.

In: Molecular BioSystems, Vol. 11, No. 8, 26.05.2015, p. 2263-2272.

Research output: Contribution to journalArticle

Parenti, MD, Bruzzone, S, Nencioni, A & Del Rio, A 2015, 'Selectivity hot-spots of sirtuin catalytic cores', Molecular BioSystems, vol. 11, no. 8, pp. 2263-2272. https://doi.org/10.1039/c5mb00205b
Parenti, Marco Daniele ; Bruzzone, Santina ; Nencioni, Alessio ; Del Rio, Alberto. / Selectivity hot-spots of sirtuin catalytic cores. In: Molecular BioSystems. 2015 ; Vol. 11, No. 8. pp. 2263-2272.
@article{eab45135345e441b978e0377a3568e23,
title = "Selectivity hot-spots of sirtuin catalytic cores",
abstract = "Sirtuins are NAD+-dependent deacetylases with several biological roles in DNA regulation, genomic stability, metabolism, longevity and immune cell functions. Numerous disease conditions are linked to sirtuins including metabolic disorders, inflammatory and autoimmune processes and cancer. Although few specific small molecule modulators have been reported to date, the need to identify selective ligands would be crucial not only for the development of active pharmaceutical ingredients for new targeted therapies but also as a tool for dissecting the biological roles of sirtuin family members. Herein, we report a comprehensive study aimed to classify and identify the selectivity hot-spots for targeting the catalytic cores of human sirtuins using small molecule modulators. Our selectivity analysis suggests that catalytic cores can be divided into different clusters that can constitute the basis for the development of selective ligands. The ensemble of hot-spot information is expected to be helpful to devise new selective chemicals targeting sirtuin family members.",
author = "Parenti, {Marco Daniele} and Santina Bruzzone and Alessio Nencioni and {Del Rio}, Alberto",
year = "2015",
month = "5",
day = "26",
doi = "10.1039/c5mb00205b",
language = "English",
volume = "11",
pages = "2263--2272",
journal = "Molecular BioSystems",
issn = "1742-206X",
publisher = "Royal Society of Chemistry",
number = "8",

}

TY - JOUR

T1 - Selectivity hot-spots of sirtuin catalytic cores

AU - Parenti, Marco Daniele

AU - Bruzzone, Santina

AU - Nencioni, Alessio

AU - Del Rio, Alberto

PY - 2015/5/26

Y1 - 2015/5/26

N2 - Sirtuins are NAD+-dependent deacetylases with several biological roles in DNA regulation, genomic stability, metabolism, longevity and immune cell functions. Numerous disease conditions are linked to sirtuins including metabolic disorders, inflammatory and autoimmune processes and cancer. Although few specific small molecule modulators have been reported to date, the need to identify selective ligands would be crucial not only for the development of active pharmaceutical ingredients for new targeted therapies but also as a tool for dissecting the biological roles of sirtuin family members. Herein, we report a comprehensive study aimed to classify and identify the selectivity hot-spots for targeting the catalytic cores of human sirtuins using small molecule modulators. Our selectivity analysis suggests that catalytic cores can be divided into different clusters that can constitute the basis for the development of selective ligands. The ensemble of hot-spot information is expected to be helpful to devise new selective chemicals targeting sirtuin family members.

AB - Sirtuins are NAD+-dependent deacetylases with several biological roles in DNA regulation, genomic stability, metabolism, longevity and immune cell functions. Numerous disease conditions are linked to sirtuins including metabolic disorders, inflammatory and autoimmune processes and cancer. Although few specific small molecule modulators have been reported to date, the need to identify selective ligands would be crucial not only for the development of active pharmaceutical ingredients for new targeted therapies but also as a tool for dissecting the biological roles of sirtuin family members. Herein, we report a comprehensive study aimed to classify and identify the selectivity hot-spots for targeting the catalytic cores of human sirtuins using small molecule modulators. Our selectivity analysis suggests that catalytic cores can be divided into different clusters that can constitute the basis for the development of selective ligands. The ensemble of hot-spot information is expected to be helpful to devise new selective chemicals targeting sirtuin family members.

UR - http://www.scopus.com/inward/record.url?scp=84940198838&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84940198838&partnerID=8YFLogxK

U2 - 10.1039/c5mb00205b

DO - 10.1039/c5mb00205b

M3 - Article

C2 - 26061123

AN - SCOPUS:84940198838

VL - 11

SP - 2263

EP - 2272

JO - Molecular BioSystems

JF - Molecular BioSystems

SN - 1742-206X

IS - 8

ER -