Muriel Bonnet1, Jack U Flanagan2, Denise A Chan3, Amato J Giaccia3, Michael P Hay4. 1. Auckland Cancer Society Research Centre, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand. 2. Auckland Cancer Society Research Centre, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland, New Zealand. 3. Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA. 4. Auckland Cancer Society Research Centre, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland, New Zealand. Electronic address: m.hay@auckland.ac.nz.
Abstract
Two novel scaffolds, 4-pyridylanilinothiazoles (PAT) and 3-pyridylphenylsulfonyl benzamides (PPB), previously identified as selective cytotoxins for von Hippel-Lindau-deficient Renal Carcinoma cells, were used as templates to prepare affinity chromatography reagents to aid the identification of the molecular targets of these two classes. Structure-activity data and computational models were used to predict possible points of attachment for linker chains. In the PAT class, Click coupling of long chain azides with 2- and 3-pyridylanilinothiazoleacetylenes gave triazole-linked pyridylanilinothiazoles which did not retain the VHL-dependent selectivity of parent analogues. For the PPB class, Sonagashira coupling of 4-iodo-(3-pyridylphenylsulfonyl)benzamide with a propargyl hexaethylene glycol carbamate gave an acetylene which was reduced to the corresponding alkyl 3-pyridylphenylsulfonylbenzamide. This reagent retained the VHL-dependent selectivity of the parent analogues and was successfully utilized as an affinity reagent.
Two novel scaffolds, 4-pyridylanilinothiazoles (n class="Chemical">PAT) and 3-pyridylphenylsulfonyl benzamides (PPB), previously identified as selective cytotoxins for von Hippel-Lindau-deficient Renal Carcinoma cells, were used as templates to prepare affinity chromatography reagents to aid the identification of the molecular targets of these two classes. Structure-activity data and computational models were used to predict possible points of attachment for linker chains. In the PAT class, Click coupling of long chain azides with 2- and 3-pyridylanilinothiazoleacetylenes gave triazole-linked pyridylanilinothiazoles which did not retain the VHL-dependent selectivity of parent analogues. For the PPB class, Sonagashira coupling of 4-iodo-(3-pyridylphenylsulfonyl)benzamide with a propargyl hexaethylene glycol carbamate gave an acetylene which was reduced to the corresponding alkyl 3-pyridylphenylsulfonylbenzamide. This reagent retained the VHL-dependent selectivity of the parent analogues and was successfully utilized as an affinity reagent.
Authors: Denise A Chan; Patrick D Sutphin; Phuong Nguyen; Sandra Turcotte; Edwin W Lai; Alice Banh; Gloria E Reynolds; Jen-Tsan Chi; Jason Wu; David E Solow-Cordero; Muriel Bonnet; Jack U Flanagan; Donna M Bouley; Edward E Graves; William A Denny; Michael P Hay; Amato J Giaccia Journal: Sci Transl Med Date: 2011-08-03 Impact factor: 17.956
Authors: Eric Jonasch; P Andrew Futreal; Ian J Davis; Sean T Bailey; William Y Kim; James Brugarolas; Amato J Giaccia; Ghada Kurban; Armin Pause; Judith Frydman; Amado J Zurita; Brian I Rini; Pam Sharma; Michael B Atkins; Cheryl L Walker; W Kimryn Rathmell Journal: Mol Cancer Res Date: 2012-05-25 Impact factor: 5.852
Authors: Lucien N Lameijer; Daniël Ernst; Samantha L Hopkins; Michael S Meijer; Sven H C Askes; Sylvia E Le Dévédec; Sylvestre Bonnet Journal: Angew Chem Int Ed Engl Date: 2017-08-09 Impact factor: 15.336