Native Zinc Catalyzes Selective and Traceless Release of Small Molecules in ß-Cells.
J Am Chem Soc
; 142(14): 6477-6482, 2020 04 08.
Article
em En
| MEDLINE
| ID: mdl-32175731
ABSTRACT
The loss of insulin-producing ß-cells is the central pathological event in type 1 and 2 diabetes, which has led to efforts to identify molecules to promote ß-cell proliferation, protection, and imaging. However, the lack of ß-cell specificity of these molecules jeopardizes their therapeutic potential. A general platform for selective release of small-molecule cargoes in ß-cells over other islet cells ex vivo or other cell-types in an organismal context will be immensely valuable in advancing diabetes research and therapeutic development. Here, we leverage the unusually high Zn(II) concentration in ß-cells to develop a Zn(II)-based prodrug system to selectively and tracelessly deliver bioactive small molecules and fluorophores to ß-cells. The Zn(II)-targeting mechanism enriches the inactive cargo in ß-cells as compared to other pancreatic cells; importantly, Zn(II)-mediated hydrolysis triggers cargo activation. This prodrug system, with modular components that allow for fine-tuning selectivity, should enable the safer and more effective targeting of ß-cells.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Zinco
/
Linfócitos B
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Diabetes Mellitus Tipo 1
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Diabetes Mellitus Tipo 2
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos