Chemical Engineering of Transcription Factors Uncovered Cell-Permeable μMax Modulators.

ABSTRACT: Transcription factor engineering has emerged as a powerful strategy for generating novel proteins for fundamental research and biomedical applications. Although various analogs have been developed, they remain largely constrained to native sequences and structures. The generation of advanced analogs bearing noncanonical modifications with enhanced functional properties remains limited. Here we combined rational design with total synthesis to engineer novel abiotic transcription factors with enhanced stability and cell permeability. Using solid-phase synthesis and native chemical ligation, we created a library of 30 Max-derived transcription factor analogs incorporating novel modifications, such as sequence mutations and aromatic staples at strategic sites. Through DNA-binding analysis and

SUBMITTER: Harel O 

PROVIDER: S-EPMC12636033 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature