title: Design and modular parallel synthesis of a MCR derived alpha-helix mimetic protein-protein interaction inhibitor scaffold.
abstract: A terphenyl alpha-helix mimetic scaffold recognized to be capable of disrupting protein-protein interactions was structurally morphed into an easily amenable and versatile multicomponent reaction (MCR) backbone. The design, modular in-parallel library synthesis, initial cell based biological data, and preliminary in vitro screening for the disruption of the Bcl-w/Bak protein-protein interaction by representatives of the MCR derived scaffold are presented.
authors.affiliation: ABC Pharma, Franckensteinstrasse 9a, 81243 München, Germany.
authors.forename: Walfrido
authors.initials: W
authors.lastname: Antuch
authors.forename: Sanjay
authors.initials: S
authors.lastname: Menon
authors.forename: Quin-Zene
authors.initials: QZ
authors.lastname: Chen
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Lu
authors.forename: Sukumar
authors.initials: S
authors.lastname: Sakamuri
authors.forename: Barbara
authors.initials: B
authors.lastname: Beck
authors.forename: Vesna
authors.initials: V
authors.lastname: Schauer-Vukasinović
authors.forename: Seema
authors.initials: S
authors.lastname: Agarwal
authors.forename: Sibylle
authors.initials: S
authors.lastname: Hess
authors.forename: Alexander
authors.initials: A
authors.lastname: Dömling
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins; D001665:Binding Sites; D040761:Biomimetic Materials / Q000737:chemistry*; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D011506:Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000037:antagonists & inhibitors / Q000378:metabolism; D051020:bcl-X Protein / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C494772:BAK1 protein, human; C491073:BCL2L2 protein, human; D007093:Imidazoles; D010446:Peptide Fragments; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051020:bcl-X Protein