Photoswitchable PROTACs for Reversible and Spatiotemporal Regulation of NAMPT and NAD.
Angew Chem Int Ed Engl
; 63(12): e202315997, 2024 03 18.
Article
en En
| MEDLINE
| ID: mdl-38282119
ABSTRACT
Nicotinamide adenine dinucleotide (NAD+ ) is an essential coenzyme with diverse biological functions in DNA synthesis. Nicotinamide phosphoribosyltransferase (NAMPT) is a key rate-limiting enzyme involved in NAD+ biosynthesis in mammals. We developed the first chemical tool for optical control of NAMPT and NAD+ in biological systems using photoswitchable proteolysis-targeting chimeras (PS-PROTACs). An NAMPT activator and dimethylpyrazolazobenzene photoswitch were used to design highly efficient PS-PROTACs, enabling up- and down-reversible regulation of NAMPT and NAD+ in a light-dependent manner and reducing the toxicity associated with inhibitor-based PS-PROTACs. PS-PROTAC was activated under 620â
nm irradiation, realizing in vivo optical manipulation of antitumor activity, NAMPT, and NAD+ .
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Nicotinamida Fosforribosiltransferasa
/
NAD
Límite:
Animals
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Año:
2024
Tipo del documento:
Article
País de afiliación:
China