Aza-peptide aldehydes and ketones: synthesis and evaluation as human 20S proteasome inhibitors.

ABSTRACT:

Aims

Aza-peptide aldehydes and ketones were developed as a new class of peptidyl analogues to inhibit the human constitutive (c)20S proteasome as alternative therapeutics to treat multiple myeloma (MM).

Material and methods

Eleven new aza-peptide aldehydes and ketones were designed based on their preference to bind at the ß5 catalytic subunit of c20S proteasome with benzyloxycarbonyl(Cbz)-Leu-Leu-Leu (MG132-like) and morpholinyl(Mp)-Homophenylalanyl(HPh)-Leu-Phe-Leu (Carfilzomib-like) sequences, synthesized, structurally characterized and evaluated for their inhibitory potency in competitive kinetic assays in vitro. Additionally, cell viability assays and molecular modeling experiments were designed and performed in support.

Results

Aza-peptide aldehydes and ketones g

SUBMITTER: Corrigan TS 

PROVIDER: S-EPMC12536793 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature