Peptide based macrocycles: selective histone deacetylase inhibitors with antiproliferative activity.

Abstract

Histone deacetylase inhibitors (HDACi) have been enthusiastically investigated as a novel generation of chemotherapeutics for cancers usually called as epigenetic therapeutics. Histone deacetylases have been found to influence cellular function by catalyzing the removal of acetyl groups from ε-N-acetylated lysine residues of several protein substrates including histones, transcription factors, α-tubulin, and nuclear importers. Cyclic peptides represent the most structurally complicated and diverse class of histone deacetylase inhibitors. Each subtype of the Histone Deacetylase (HDAC) family perform a distinct role in the gene expression and cyclic peptides with their plentiful set of surface contacts, zinc binding group and macrocyclic cap, can target enzyme precisely through adequate modulation of the amino acid configurational and structural assortment. The present article summarizes current status of different peptide based macrocyclic compounds being developed as HDACi for the treatment of cancer.

• Authors: H Rajak, A Singh, P K Dewangan, V Patel, D K Jain, S K Tiwari, R Veerasamy, P C Sharma
• Journal: Current medicinal chemistry (Curr Med Chem) Vol. 20 Issue 14 Pg. 1887-903 ( 2013) ISSN: 1875-533X [Electronic] United Arab Emirates
• PMID: 23409715 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antineoplastic Agents
• Histone Deacetylase Inhibitors
• Macrocyclic Compounds
• Peptides, Cyclic

Topics

• Antineoplastic Agents (chemistry, pharmacology)
• Histone Deacetylase Inhibitors (chemistry, pharmacology)
• Humans
• Macrocyclic Compounds (chemistry, pharmacology)
• Neoplasms (drug therapy, enzymology)
• Peptides, Cyclic (chemistry, pharmacology)