A cell permeable bimane-constrained PCNA-interacting peptide.

ABSTRACT: The human sliding clamp protein known as proliferating cell nuclear antigen (PCNA) orchestrates DNA-replication and -repair and as such is an ideal therapeutic target for proliferative diseases, including cancer. Peptides derived from the human p21 protein bind PCNA with high affinity via a 3₁₀-helical binding conformation and are known to shut down DNA-replication. Here, we present studies on short analogues of p21 peptides (143-151) conformationally constrained with a covalent linker between i, i + 4 separated cysteine residues at positions 145 and 149 to access peptidomimetics that target PCNA. The resulting macrocycles bind PCNA with K _D values ranging from 570 nM to 3.86 μM, with the bimane-constrained peptide 7 proving the most

SUBMITTER: Horsfall AJ 

PROVIDER: S-EPMC8496261 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature