title: Peptides and Pseudopeptides as SIRT6 Deacetylation Inhibitors.
abstract: SIRT6 belongs to the family of histone deacetylases (class III), but it also has mono-ADP-ribosyltransferase activity. SIRT6 is a nuclear sirtuin that has been associated with aging, cellular protection, and sugar metabolism. Despite these important roles for SIRT6, thus far, there are only a few weak SIRT6 inhibitors available, and no structure-activity relationship (SAR) studies have been published. This is the first study concerning peptides and pseudopeptides as SIRT6 deacetylation inhibitors and the first SAR data concerning SIRT6. We also investigated the molecular interactions using a homology model. We report three compounds exhibiting 62-91% SIRT6 inhibition at 200 μM concentration. These compounds can serve as starting points for systematic SAR studies and SIRT6 inhibitor design.
authors.affiliation: School of Pharmacy, University of Eastern Finland , P.O. Box 1627, 70211 Kuopio, Finland.
authors.forename: Piia
authors.initials: P
authors.lastname: Kokkonen
authors.affiliation: School of Pharmacy, University of Eastern Finland , P.O. Box 1627, 70211 Kuopio, Finland.
authors.forename: Minna
authors.initials: M
authors.lastname: Rahnasto-Rilla
authors.affiliation: School of Pharmacy, University of Eastern Finland , P.O. Box 1627, 70211 Kuopio, Finland.
authors.forename: Päivi H
authors.initials: PH
authors.lastname: Kiviranta
authors.affiliation: School of Pharmacy, University of Eastern Finland , P.O. Box 1627, 70211 Kuopio, Finland.
authors.forename: Tero
authors.initials: T
authors.lastname: Huhtiniemi
authors.affiliation: School of Pharmacy, University of Eastern Finland , P.O. Box 1627, 70211 Kuopio, Finland.
authors.forename: Tuomo
authors.initials: T
authors.lastname: Laitinen
authors.affiliation: School of Pharmacy, University of Eastern Finland , P.O. Box 1627, 70211 Kuopio, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Poso
authors.affiliation: School of Pharmacy, University of Eastern Finland , P.O. Box 1627, 70211 Kuopio, Finland.
authors.forename: Elina
authors.initials: E
authors.lastname: Jarho
authors.affiliation: School of Pharmacy, University of Eastern Finland , P.O. Box 1627, 70211 Kuopio, Finland.
authors.forename: Maija
authors.initials: M
authors.lastname: Lahtela-Kakkonen
keywords: SIRT6; inhibitor; peptide; pseudopeptide; sirtuin; substrate-based inhibitor