1. Interaction of aliphatic cap group in inhibition of histone deacetylases by cyclic tetrapeptides
- Author
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Tomonori G. Nishino, Mohammed Bhuiyan, Gururaj M. Shivashimpi, Satoko Maeda, Minoru Yoshida, Preeti B. Soni, Tamaki Kato, and Norikazu Nishino
- Subjects
Stereochemistry ,Clinical Biochemistry ,Pharmaceutical Science ,Antineoplastic Agents ,Histone Deacetylase 1 ,Peptide ,Histone Deacetylase 6 ,Ring (chemistry) ,Peptides, Cyclic ,Biochemistry ,Histone Deacetylases ,Cell Line ,Inhibitory Concentration 50 ,Structure-Activity Relationship ,chemistry.chemical_compound ,Drug Discovery ,Peptide synthesis ,Humans ,Enzyme Inhibitors ,Molecular Biology ,chemistry.chemical_classification ,Bicyclic molecule ,Tetrapeptide ,Organic Chemistry ,Cyclic peptide ,Amino acid ,Histone Deacetylase Inhibitors ,Repressor Proteins ,chemistry ,Molecular Medicine ,Histone deacetylase - Abstract
Inhibitors of histone deacetylases (HDACs) are a promising class of anticancer agents that effect gene regulation. To know the interaction of aliphatic cap groups with HDACs, cyclic tetrapeptide and bicyclic peptide disulfide hybrids were synthesized without aromatic ring in their macrocyclic framework. Benzene ring of l -Phe in chlamydocin was replaced with several aliphatic amino acids and also a fused bicyclic tetrapeptide was synthesized by ring closing metathesis using Grubb’s first generation catalyst. The inhibitory activities of the cyclic peptides against histone deacetylase enzymes were evaluated, which demonstrated most of them are interesting candidates as anticancer agents.
- Published
- 2008
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