Affinity-matured DLL4 ligands as broad-spectrum modulators of Notch signaling.

ABSTRACT: The Notch pathway regulates cell fate decisions and is an emerging target for regenerative and cancer therapies. Recombinant Notch ligands are attractive candidates for modulating Notch signaling; however, their intrinsically low receptor-binding affinity restricts their utility in biomedical applications. To overcome this limitation, we evolved variants of the ligand Delta-like 4 with enhanced affinity and cross-reactivity. A consensus variant with maximized binding affinity, Delta^MAX, binds human and murine Notch receptors with 500- to 1,000-fold increased affinity compared with wild-type human Delta-like 4. Delta^MAX also potently activates Notch in plate-bound, bead-bound and cellular formats. When administered as a soluble decoy, Delta^MAX inhibits Notch

SUBMITTER: Gonzalez-Perez D 

PROVIDER: S-EPMC10132381 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature