Peptidomimetics Targeting the Amyloidogenicity of Nucleophosmin 1 Mutations in Acute Myeloid Leukemia.

ABSTRACT: Nucleophosmin 1(NPM1) is an abundant human protein endowed with many functions where whose dysregulation leads to various cancers and mutations are relevant in acute myeloid leukemia (AML). In the wild-type form, pentameric NPM1 resides mainly in the nucleolus even if it shuttles toward the cytosol exerting its chaperon function; conversely in AML-mutated versions, it has mainly a cytoplasmic localization, hence the name NPMc+. All types of AML mutations determine an important amyloid aggregation propensity of the C-terminal domains (CTD) of NPMc+ and to exploit this amyloidogenicity for therapeutical purposes; herein, this study presents the design and structural and functional investigations of a series of peptides analogs of the sequence of the second helix of the three-helix bundle of

SUBMITTER: Florio D 

PROVIDER: S-EPMC12278350 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature