title: Relaxation of the rigid backbone of an oligoamide-foldamer-based α-helix mimetic: identification of potent Bcl-xL inhibitors.
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.
authors.affiliation: Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 N Pine St, Baltimore, MD 21201, USA.
authors.forename: Jeremy L
authors.initials: JL
authors.lastname: Yap
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Cao
authors.forename: Kenno
authors.initials: K
authors.lastname: Vanommeslaeghe
authors.forename: Kwan-Young
authors.initials: KY
authors.lastname: Jung
authors.forename: Chander
authors.initials: C
authors.lastname: Peddaboina
authors.forename: Paul T
authors.initials: PT
authors.lastname: Wilder
authors.forename: Anjan
authors.initials: A
authors.lastname: Nan
authors.forename: Alexander D
authors.initials: AD
authors.lastname: MacKerell
authors.forename: W Roy
authors.initials: WR
authors.lastname: Smythe
authors.forename: Steven
authors.initials: S
authors.lastname: Fletcher
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides / Q000138:chemical synthesis* / Q000494:pharmacology; D001665:Binding Sites; D040761:Biomimetic Materials / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D006801:Humans; D006860:Hydrogen Bonding; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry; D010848:Picolinic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000737:chemistry; D051020:bcl-X Protein / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D000577:Amides; D000970:Antineoplastic Agents; D001549:Benzamides; D010446:Peptide Fragments; D010848:Picolinic Acids; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051020:bcl-X Protein; C003142:picolinamide