389127-43-9Relevant articles and documents
Structure-Enabled Discovery of a Stapled Peptide Inhibitor to Target the Oncogenic Transcriptional Repressor TLE1
McGrath, Sally,Tortorici, Marcello,Drouin, Ludovic,Solanki, Savade,Vidler, Lewis,Westwood, Isaac,Gimeson, Peter,Van Montfort, Rob,Hoelder, Swen
, p. 9577 - 9584 (2017/07/22)
TLE1 is an oncogenic transcriptional co-repressor that exerts its repressive effects through binding of transcription factors. Inhibition of this protein–protein interaction represents a putative cancer target, but no small-molecule inhibitors have been published for this challenging interface. Herein, the structure-enabled design and synthesis of a constrained peptide inhibitor of TLE1 is reported. The design features the introduction of a four-carbon-atom linker into the peptide epitope found in many TLE1 binding partners. A concise synthetic route to a proof-of-concept peptide, cycFWRPW, has been developed. Biophysical testing by isothermal titration calorimetry and thermal shift assays showed that, although the constrained peptide bound potently, it had an approximately five-fold higher Kd than that of the unconstrained peptide. The co-crystal structure suggested that the reduced affinity was likely to be due to a small shift of one side chain, relative to the otherwise well-conserved conformation of the acyclic peptide. This work describes a constrained peptide inhibitor that may serve as the basis for improved inhibitors.
Design, synthesis, and biological evaluation of new monoamine reuptake inhibitors with potential therapeutic utility in depression and pain
Lucas, Matthew C.,Weikert, Robert J.,Carter, David S.,Cai, Hai-Ying,Greenhouse, Robert,Iyer, Pravin S.,Lin, Clara J.,Lee, Eun Kyung,Madera, Ann Marie,Moore, Amy,Ozboya, Kerem,Schoenfeld, Ryan C.,Steiner, Sandra,Zhai, Yansheng,Lynch, Stephen M.
scheme or table, p. 5559 - 5566 (2011/02/22)
Two new series of monoamine triple reuptake inhibitors (TRIs) have been discovered through scaffold homologation of our recently reported series of 3,3-disubstituted pyrrolidine TRIs. The regioisomeric 2- and 3-ketopyrrolidines demonstrated high levels of
Enantioselective total synthesis of avrainvillamide and the stephacidins
Baran, Phil S.,Hafensteiner, Benjamin D.,Ambhaikar, Narendra B.,Guerrero, Carlos A.,Gallagher, John D.
, p. 8678 - 8693 (2007/10/03)
In this article, full details regarding our total synthesis of avrainvillamide and the stephacidins are presented. After an introduction and summary of prior synthetic studies in this family of structurally complex anticancer natural products, the evoluti
Rational molecular design and EPC synthesis of a type VI β-turn inducing peptide mimetic
Hoffmann, Tobias,Lanig, Harald,Waibel, Reiner,Gmeiner, Peter
, p. 3361 - 3364 (2007/10/03)
A fruitful combination of molecular dynamics based design and modern synthetic reactions led to a conformatively rigidized cis-peptidyl proline surrogate (see picture). NMR spectroscopic experiments clearly show the existance of type VIa β-turn properties
