Abstract |
A set of azapeptides was designed based on the Ala-Val- Pro-Ile peptide (derived from Smac protein) to activate caspase-9 and induce apoptosis in breast cancer cells. The diversity-oriented synthesis of the aza- peptides 5-9 was accomplished by alkylation of the aza-residue of aza-Gly-Pro dipeptide 15 using potassium tert-butoxide and a range of different alkyl halides. The resulting protected aza- dipeptide building blocks were then introduced into mimics 5-9 using standard coupling conditions. Biological evaluation of 5-9 was performed in MDA-MB-231 breast cancer cells, and indicated that the aza-Gly and aza-Phe analogs 5 and 7 were most efficient in inducing cell death by a caspase-9 mediated apoptotic pathway. Revealing a relationship between azabicycloalkanone and aza peptide mimics, novel AVPI mimics were synthesized which exhibit utility for studying structure-activity relationships to develop leads for activating apoptosis in cancer cells.
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Authors | Carine B Bourguet, Pierre-Luc Boulay, Audrey Claing, William D Lubell |
Journal | Bioorganic & medicinal chemistry letters
(Bioorg Med Chem Lett)
Vol. 24
Issue 15
Pg. 3361-5
(Aug 01 2014)
ISSN: 1464-3405 [Electronic] England |
PMID | 24986663
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2014 Elsevier Ltd. All rights reserved. |
Chemical References |
- Antineoplastic Agents
- Aza Compounds
- Oligopeptides
- Caspase 9
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Topics |
- Antineoplastic Agents
(chemical synthesis, chemistry, pharmacology)
- Apoptosis
(drug effects)
- Aza Compounds
(chemical synthesis, chemistry, pharmacology)
- Breast Neoplasms
(drug therapy, metabolism, pathology)
- Caspase 9
(metabolism)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Dose-Response Relationship, Drug
- Drug Design
- Drug Screening Assays, Antitumor
- Humans
- Molecular Structure
- Oligopeptides
(chemical synthesis, chemistry, pharmacology)
- Structure-Activity Relationship
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