Engineered coiled-coil HIF1α protein domain mimic.
Biomater Sci
; 12(11): 2951-2959, 2024 May 28.
Article
em En
| MEDLINE
| ID: mdl-38656316
ABSTRACT
The development of targeted anti-cancer therapeutics offers the potential for increased efficacy of drugs and diagnostics. Utilizing modalities agnostic to tumor type, such as the hypoxic tumor microenvironment (TME), may assist in the development of universal tumor targeting agents. The hypoxia-inducible factor (HIF), in particular HIF1, plays a key role in tumor adaptation to hypoxia, and inhibiting its interaction with p300 has been shown to provide therapeutic potential. Using a multivalent assembled protein (MAP) approach based on the self-assembly of the cartilage oligomeric matrix protein coiled-coil (COMPcc) domain fused to the critical residues of the C-terminal transactivation domain (C-TAD) of the α subunit of HIF1 (HIF1α), we generate HIF1α-MAP (H-MAP). The resulting H-MAP demonstrates picomolar binding affinity to p300, the ability to downregulate hypoxia-inducible genes, and in vivo tumor targeting capability.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Engenharia de Proteínas
/
Subunidade alfa do Fator 1 Induzível por Hipóxia
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Biomater Sci
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos