Design, synthesis and properties of peptide inhibitors based on BRCA1856-871

Guangming Sun; Yi Zhao; Libo Yuan; Kui Lu

doi:10.1016/j.bmcl.2022.128859

Design, synthesis and properties of peptide inhibitors based on BRCA1^856-871

Bioorg Med Chem Lett. 2022 Sep 15:72:128859. doi: 10.1016/j.bmcl.2022.128859. Epub 2022 Jun 15.

Authors

Guangming Sun¹, Yi Zhao¹, Libo Yuan², Kui Lu³

Affiliations

¹ College of Chemistry, Zhengzhou University, Zhengzhou 450001, China; College of Chemistry and Chemical Engineering, Henan University of Technology, Zhengzhou 450001, China.
² College of Chemistry and Chemical Engineering, Henan University of Technology, Zhengzhou 450001, China.
³ School of Chemical Engineering and Food Science, Zhengzhou University of Technology, School of Chemical Engineering and Food Science, Zhengzhou University of Technology, Zhengzhou 450044, China. Electronic address: lukui126@126.com.

PMID: 35716865
DOI: 10.1016/j.bmcl.2022.128859

Abstract

Overexpression of RAD51 protein was found to increase drug resistance in breast cancer cells. Breast cancer susceptibility gene 1 (BRCA1) protein can specifically bind to RAD51 protein and regulate the expression level of RAD51 protein. Based on previous studies, eight modified peptides were obtained by modifying the N-terminus of the key peptide segment 856-871 of BRCA1 with nicotinic acid (NA) and its derivatives. The interaction of BRCA1^856-871 and modified peptides with the RAD51^158-180 target peptide was investigated by fluorescence and circular dichroism spectroscopies. The results showed that the binding ability of 2-TFM-NA-PP to RAD51^158-180 was significantly enhanced. BRCA1^856-871 and modified peptides were studied by in vitro cell experiments. The results showed that the antitumor activity of 5-TFM-NA-PP was significantly enhanced compared with BRCA1^856-871.

Keywords: BRCA1 RAD51 Nicotinic Acid (NA).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

BRCA1 Protein / genetics
BRCA2 Protein / genetics
Breast Neoplasms*
Female
Genes, BRCA1
Humans
Peptides / pharmacology
Rad51 Recombinase*

Substances

BRCA1 Protein
BRCA1 protein, human
BRCA2 Protein
Peptides
Rad51 Recombinase