Engineered apoptosis-inducing peptides with enhanced mitochondrial localization and potency
| Autor: | Kristin L. Horton, Shana O. Kelley |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
medicine.medical_specialty
Peptide Antineoplastic Agents Apoptosis Mitochondrion Protein Engineering Internal medicine Cell Line Tumor Drug Discovery medicine Potency Humans Amino Acid Sequence Cytotoxicity Peptide sequence chemistry.chemical_classification Oligopeptide Dose-Response Relationship Drug Chemistry Protein engineering Cell biology Mitochondria Endocrinology Mechanism of action Molecular Medicine medicine.symptom Oligopeptides |
| Zdroj: | Journal of medicinal chemistry. 52(10) |
| ISSN: | 1520-4804 |
| Popis: | Apoptosis-inducing peptides that trigger mitochondrial disruption are a popular tool in pharmaceutical and anticancer research. While useful, their potencies are low, which impedes further development of drugs based on these sequences. Here, we describe an effort to engineer the intracellular localization and activity of a peptide with known anticancer activity, D-(KLAKLAK)(2), to improve potency by increasing the specificity of the peptide for mitochondria and enhancing disruption of this organelle. The engineered peptides are significantly more toxic to a wide variety of cancer cell lines, with the best analogue exhibiting a LC(50) value 100-fold lower than the parent compound. Importantly, the peptides maintain their potency when made cell-type specific. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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