Configuration of two cysteine residues in a ring within a stapled Bim peptide affects the secondary structure and apoptotic activity

Shengli Zhou; Fuka Nishimura; Kazuhaya Wada; Kaho Fujii; Takeshi Kondo; Kazunori Watanabe; Yoshitane Imai; Takashi Ohtsuki; Mizuki Kitamatsu

doi:10.1016/j.bmcl.2024.129915

Configuration of two cysteine residues in a ring within a stapled Bim peptide affects the secondary structure and apoptotic activity

Bioorg Med Chem Lett. 2024 Nov 1:112:129915. doi: 10.1016/j.bmcl.2024.129915. Epub 2024 Aug 9.

Authors

Shengli Zhou¹, Fuka Nishimura², Kazuhaya Wada², Kaho Fujii², Takeshi Kondo², Kazunori Watanabe¹, Yoshitane Imai², Takashi Ohtsuki³, Mizuki Kitamatsu⁴

Affiliations

¹ Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University, 3-1-1 Tsushimanaka, Okayama 700-8530, Japan.
² Department of Applied Chemistry, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan.
³ Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University, 3-1-1 Tsushimanaka, Okayama 700-8530, Japan. Electronic address: [email protected].
⁴ Department of Applied Chemistry, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan. Electronic address: [email protected].

PMID: 39127242
DOI: 10.1016/j.bmcl.2024.129915

Abstract

Many reports have shown that stabilization of secondary structure by stapling functional peptides enhances the intracellular bioactivity. However, no report has discussed the correlation between stabilization and biological activity based on the configuration of amino acid residues used as anchors for stapling. To clarify this, we investigated the helix content and apoptotic efficiency of an apoptosis-inducing peptide, Bim, and four stapled Bim peptides containing stapling-related Cys residues introduced with different configurations within the sequence. The results demonstrated that the configuration of Cys residues in stapled Bim peptides affected the secondary structure and intracellular activity of the peptides, and furthermore, there was a correlation between these latter two variables.

Keywords: Apoptosis; Bim peptide; Cell-penetrating peptide; Intracellular delivery; Stapling.

MeSH terms

Apoptosis* / drug effects
Bcl-2-Like Protein 11* / chemistry
Bcl-2-Like Protein 11* / metabolism
Cysteine* / chemistry
Humans
Peptides* / chemical synthesis
Peptides* / chemistry
Peptides* / pharmacology
Protein Structure, Secondary*
Structure-Activity Relationship

Substances

Cysteine
Bcl-2-Like Protein 11
Peptides