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Bioorg Med Chem Lett ; 112: 129915, 2024 Nov 01.
Article in English | MEDLINE | ID: mdl-39127242

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.


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