Relaxation of the rigid backbone of an oligoamide-foldamer-based α-helix mimetic: identification of potent Bcl-xL inhibitors.

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TitleRelaxation of the rigid backbone of an oligoamide-foldamer-based α-helix mimetic: identification of potent Bcl-xL inhibitors.
Publication TypeJournal Article
Year of Publication2012
AuthorsYap, JL, Cao, X, Vanommeslaeghe, K, Jung, K-Y, Peddaboina, C, Wilder, PT, Nan, A, Mackerell, AD, W Smythe, R, Fletcher, S
JournalOrg Biomol Chem
Volume10
Issue15
Pagination2928-33
Date Published2012 Apr 21
ISSN1477-0539
KeywordsAmides, Antineoplastic Agents, Apoptosis, bcl-2 Homologous Antagonist-Killer Protein, bcl-X Protein, Benzamides, Binding Sites, Biomimetic Materials, Cell Line, Tumor, Humans, Hydrogen Bonding, Inhibitory Concentration 50, Magnetic Resonance Spectroscopy, Models, Molecular, Peptide Fragments, Picolinic Acids, Protein Binding, Protein Structure, Tertiary, Structure-Activity Relationship, Thermodynamics
Abstract

By conducting a structure-activity relationship study of the backbone of a series of oligoamide-foldamer-based α-helix mimetics of the Bak BH3 helix, we have identified especially potent inhibitors of Bcl-x(L). The most potent compound has a K(i) value of 94 nM in vitro, and single-digit micromolar IC(50) values against the proliferation of several Bcl-x(L)-overexpressing cancer cell lines.

DOI10.1039/c2ob07125h
Alternate JournalOrg. Biomol. Chem.
PubMed ID22395339