Synthesis of biotinylated photoaffinity probes based on arylsulfonamide γ-secretase inhibitors

Synthesis and biological evaluation of an arylsulfonamide class of gamma-secretase inhibitors are described. Design, synthesis, and biological evaluation of multifunctional molecular probes harboring a benzophenone photophore as a cross-linking group and a biotin tag are also reported.

[1]  Y. Tohda,et al.  A convenient synthesis of acetylenes: catalytic substitutions of acetylenic hydrogen with bromoalkenes, iodoarenes and bromopyridines , 1975 .

[2]  T. Iwatsubo,et al.  The role of presenilin cofactors in the γ-secretase complex , 2003, Nature.

[3]  Maurice Goeldner,et al.  Recent Trends in Photoaffinity Labeling , 1995 .

[4]  J. Treanor,et al.  Fenchylamine sulfonamide inhibitors of amyloid beta peptide production by the gamma-secretase proteolytic pathway: potential small-molecule therapeutic agents for the treatment of Alzheimer's disease. , 2000, Journal of medicinal chemistry.

[5]  L. Tarassishin,et al.  Stereoselective Synthesis of Photoreactive Peptidomimetic γ-Secretase Inhibitors , 2004 .

[6]  David W. Smith,et al.  Dynamics of β-Amyloid Reductions in Brain, Cerebrospinal Fluid, and Plasma of β-Amyloid Precursor Protein Transgenic Mice Treated with a γ-Secretase Inhibitor , 2005, Journal of Pharmacology and Experimental Therapeutics.

[7]  C. Haass,et al.  A γ‐secretase inhibitor blocks Notch signaling in vivo and causes a severe neurogenic phenotype in zebrafish , 2002, EMBO reports.

[8]  Jay S. Fine,et al.  Chronic Treatment with the γ-Secretase Inhibitor LY-411,575 Inhibits β-Amyloid Peptide Production and Alters Lymphopoiesis and Intestinal Cell Differentiation* , 2004, Journal of Biological Chemistry.

[9]  Min Xu,et al.  Photoactivated γ-secretase inhibitors directed to the active site covalently label presenilin 1 , 2000, Nature.

[10]  P. Knochel,et al.  Functionalized magnesium organometallics as versatile intermediates for the synthesis of polyfunctional heterocycles. , 2006, Chemical communications.

[11]  T. Iwatsubo,et al.  Highly efficient synthesis of medium-sized lactams via intramolecular Staudinger–aza-Wittig reaction of ω-azido pentafluorophenyl ester: synthesis and biological evaluation of LY411575 analogues , 2004 .

[12]  Gregory D. Longmore,et al.  γ-Secretase inhibitors repress thymocyte development , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[13]  D. Selkoe,et al.  Defining molecular targets to prevent Alzheimer disease. , 2005, Archives of neurology.

[14]  T. Iwatsubo,et al.  Parallel synthesis of DAPT derivatives and their γ-secretase-inhibitory activity , 2004 .

[15]  Leonid Tarassishin,et al.  Processing of Notch and amyloid precursor protein by γ-secretase is spatially distinct , 2004 .

[16]  S. Horwitz,et al.  Design, synthesis, and biological evaluation of potent discodermolide fluorescent and photoaffinity molecular probes. , 2005, Organic letters.

[17]  T. Iwatsubo,et al.  Solid-phase synthesis of photoaffinity probes: highly efficient incorporation of biotin-tag and cross-linking groups. , 2003, Chemical communications.

[18]  W. H. Jordan,et al.  Adipsin, a Biomarker of Gastrointestinal Toxicity Mediated by a Functional γ-Secretase Inhibitor* , 2003, Journal of Biological Chemistry.

[19]  B. Schmidt.  Aspartic Proteases Involved in Alzheimer's Disease , 2003, Chembiochem : a European journal of chemical biology.

[20]  Raphael Kopan,et al.  γ-Secretase activity is dispensable for mesenchyme-to-epithelium transition but required for podocyte and proximal tubule formation in developing mouse kidney , 2003, Development.

[21]  N. Perrimon,et al.  γ‐Secretase/presenilin inhibitors for Alzheimer's disease phenocopy Notch mutations in Drosophila , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[22]  Naoyuki Sugiyama,et al.  Development of Biotin–Avidin Technology to Investigate Okadaic Acid-Promoted Cell Signaling Pathway , 2000 .

[23]  K. Sonogashira,et al.  Development of Pd–Cu catalyzed cross-coupling of terminal acetylenes with sp2-carbon halides , 2002 .

[24]  N. Krause,et al.  Improved Procedures for the Palladium-Catalyzed Coupling of Terminal Alkynes with Aryl Bromides (Sonogashira Coupling)† , 1998 .

[25]  Francois Pognan,et al.  Modulation of notch processing by gamma-secretase inhibitors causes intestinal goblet cell metaplasia and induction of genes known to specify gut secretory lineage differentiation. , 2004, Toxicological sciences : an official journal of the Society of Toxicology.

[26]  M. Wolfe,et al.  The initial substrate-binding site of γ-secretase is located on presenilin near the active site , 2005 .

[27]  J. Best,et al.  A novel series of potent γ-secretase inhibitors based on a benzobicyclo[4.2.1]nonane core , 2005 .

[28]  G. Prestwich,et al.  Benzophenone photophores in biochemistry. , 1994, Biochemistry.

[29]  G. Prestwich,et al.  Using photolabile ligands in drug discovery and development. , 2000, Trends in biotechnology.

[30]  T. Iwatsubo,et al.  C-terminal Fragment of Presenilin Is the Molecular Target of a Dipeptidic γ-Secretase-specific Inhibitor DAPT (N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-Butyl Ester)* , 2006, Journal of Biological Chemistry.

[31]  T. Iwatsubo,et al.  Sulindac Sulfide Is a Noncompetitive γ-Secretase Inhibitor That Preferentially Reduces Aβ42 Generation* , 2003, The Journal of Biological Chemistry.

[32]  S. Wagner,et al.  Reductions in β-amyloid concentrations in vivo by the γ-secretase inhibitors BMS-289948 and BMS-299897 , 2005 .

[33]  O. Mitsunobu.  The Use of Diethyl Azodicarboxylate and Triphenylphosphine in Synthesis and Transformation of Natural Products , 1981 .

[34]  R. Perlmutter,et al.  Presenilin-dependent γ-secretase activity modulates thymocyte development , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[35]  T. Iwatsubo,et al.  gamma-secretase as a therapeutic target for treatment of Alzheimer's disease. , 2006, Current pharmaceutical design.