Lidia Mosyak

Summary

Affiliation: Wyeth Research
Country: USA

Publications

  1. ncbi The structure of the Lingo-1 ectodomain, a module implicated in central nervous system repair inhibition
    Lidia Mosyak
    Department of Chemical and Screening Sciences, Wyeth Research, Cambridge, Massachusetts 02140, USA
    J Biol Chem 281:36378-90. 2006
  2. pmc Crystal structures of the two major aggrecan degrading enzymes, ADAMTS4 and ADAMTS5
    Lidia Mosyak
    Department of Chemical and Screening Sciences, Wyeth Research, Cambridge, MA 02140, USA
    Protein Sci 17:16-21. 2008
  3. ncbi Structure-based optimization of PKCtheta inhibitors
    L Mosyak
    Chemical and Screening Sciences, Wyeth Research, Cambridge, MA 02140, U S A
    Biochem Soc Trans 35:1027-31. 2007
  4. ncbi Discovery of novel inhibitors of the ZipA/FtsZ complex by NMR fragment screening coupled with structure-based design
    Desiree H H Tsao
    Structural Biology and Computational Chemistry, Wyeth Research, Cambridge, MA 02140, USA
    Bioorg Med Chem 14:7953-61. 2006
  5. ncbi Combinatorial synthesis of substituted 3-(2-indolyl)piperidines and 2-phenyl indoles as inhibitors of ZipA-FtsZ interaction
    Lee D Jennings
    Wyeth Research, Department of Medicinal Chemistry, 401 N Middletown Road, Pearl River, NY 10965, USA
    Bioorg Med Chem 12:5115-31. 2004
  6. ncbi A shape-based 3-D scaffold hopping method and its application to a bacterial protein-protein interaction
    Thomas S Rush
    Department of Chemical and Screening Sciences, Wyeth Research, 87 Cambridge Park Drive, Cambridge, MA 02140, USA
    J Med Chem 48:1489-95. 2005
  7. ncbi Catalytic domain crystal structure of protein kinase C-theta (PKCtheta)
    Zhang Bao Xu
    Department of Chemical and Screening Sciences, Inflammation Department, Wyeth Research, Cambridge, Massachusetts 02140, USA
    J Biol Chem 279:50401-9. 2004
  8. ncbi Structure-based design of carboxybiphenylindole inhibitors of the ZipA-FtsZ interaction
    Alan G Sutherland
    Chemical and Screening Sciences, Wyeth Research, Pearl River, NY 10965, USA
    Org Biomol Chem 1:4138-40. 2003
  9. ncbi Design and synthesis of indolo[2,3-a]quinolizin-7-one inhibitors of the ZipA-FtsZ interaction
    Lee D Jennings
    Wyeth Research, Department of Medicinal Chemistry, 401N Middletown Rd, Pearl River, NY 10965, USA
    Bioorg Med Chem Lett 14:1427-31. 2004
  10. ncbi Crystal structure of the wild-type von Willebrand factor A1-glycoprotein Ibalpha complex reveals conformation differences with a complex bearing von Willebrand disease mutations
    John J Dumas
    Department of Chemical and Screening Sciences, Wyeth, Cambridge, Massachusetts 02140, USA
    J Biol Chem 279:23327-34. 2004

Collaborators

Detail Information

Publications22

  1. ncbi The structure of the Lingo-1 ectodomain, a module implicated in central nervous system repair inhibition
    Lidia Mosyak
    Department of Chemical and Screening Sciences, Wyeth Research, Cambridge, Massachusetts 02140, USA
    J Biol Chem 281:36378-90. 2006
    ..Potential functional binding sites that can be identified on the ectodomain surface, including the site of self-recognition, suggest a model for protein assembly on the membrane...
  2. pmc Crystal structures of the two major aggrecan degrading enzymes, ADAMTS4 and ADAMTS5
    Lidia Mosyak
    Department of Chemical and Screening Sciences, Wyeth Research, Cambridge, MA 02140, USA
    Protein Sci 17:16-21. 2008
    ..On this basis, we propose that mature aggrecanases exist as an ensemble of at least two isomers, only one of which is proteolytically active...
  3. ncbi Structure-based optimization of PKCtheta inhibitors
    L Mosyak
    Chemical and Screening Sciences, Wyeth Research, Cambridge, MA 02140, U S A
    Biochem Soc Trans 35:1027-31. 2007
    ..Here, we discuss our work on the discovery of lead chemical series and review our X-ray structural and modelling approaches, including a structure-surrogate strategy that helped guide us in the lead compound optimizations...
  4. ncbi Discovery of novel inhibitors of the ZipA/FtsZ complex by NMR fragment screening coupled with structure-based design
    Desiree H H Tsao
    Structural Biology and Computational Chemistry, Wyeth Research, Cambridge, MA 02140, USA
    Bioorg Med Chem 14:7953-61. 2006
    ..Analogs of this hit were also evaluated by NMR and X-ray crystal structures of these analogs with ZipA were obtained, providing structural information to help guide the medicinal chemistry efforts...
  5. ncbi Combinatorial synthesis of substituted 3-(2-indolyl)piperidines and 2-phenyl indoles as inhibitors of ZipA-FtsZ interaction
    Lee D Jennings
    Wyeth Research, Department of Medicinal Chemistry, 401 N Middletown Road, Pearl River, NY 10965, USA
    Bioorg Med Chem 12:5115-31. 2004
    ..Compounds were demonstrated to bind to the FtsZ binding domain of ZipA by HSQC NMR and to inhibit cell division in a cell elongation assay...
  6. ncbi A shape-based 3-D scaffold hopping method and its application to a bacterial protein-protein interaction
    Thomas S Rush
    Department of Chemical and Screening Sciences, Wyeth Research, 87 Cambridge Park Drive, Cambridge, MA 02140, USA
    J Med Chem 48:1489-95. 2005
    ..These experimental results validate this use of ROCS for chemotype switching or "lead hopping" and suggest that it is of general interest for lead identification in drug discovery endeavors...
  7. ncbi Catalytic domain crystal structure of protein kinase C-theta (PKCtheta)
    Zhang Bao Xu
    Department of Chemical and Screening Sciences, Inflammation Department, Wyeth Research, Cambridge, Massachusetts 02140, USA
    J Biol Chem 279:50401-9. 2004
    ....
  8. ncbi Structure-based design of carboxybiphenylindole inhibitors of the ZipA-FtsZ interaction
    Alan G Sutherland
    Chemical and Screening Sciences, Wyeth Research, Pearl River, NY 10965, USA
    Org Biomol Chem 1:4138-40. 2003
    ....
  9. ncbi Design and synthesis of indolo[2,3-a]quinolizin-7-one inhibitors of the ZipA-FtsZ interaction
    Lee D Jennings
    Wyeth Research, Department of Medicinal Chemistry, 401N Middletown Rd, Pearl River, NY 10965, USA
    Bioorg Med Chem Lett 14:1427-31. 2004
    ..The X-ray crystal structure of one of these molecules complexed with ZipA was solved. The structure revealed an unexpected binding mode, facilitated by desolvation of a loosely bound surface water...
  10. ncbi Crystal structure of the wild-type von Willebrand factor A1-glycoprotein Ibalpha complex reveals conformation differences with a complex bearing von Willebrand disease mutations
    John J Dumas
    Department of Chemical and Screening Sciences, Wyeth, Cambridge, Massachusetts 02140, USA
    J Biol Chem 279:23327-34. 2004
    ..These findings provide important details that add to our understanding of how both type 2B and platelet-type VWD mutations affect GpIbalpha-A1 binding affinity...
  11. doi Novel synthesis and structural characterization of a high-affinity paramagnetic kinase probe for the identification of non-ATP site binders by nuclear magnetic resonance
    Franklin J Moy
    Structural Biology and Computational Chemistry, Wyeth Research, 200 CambridgePark Drive, Cambridge, Massachusetts 02140, USA
    J Med Chem 53:1238-49. 2010
    ..We believe that this spin-labeled probe is a valuable tool that holds broad applicability in a screen for non-ATP site binders...
  12. pmc Triad of polar residues implicated in pH specificity of acidic mammalian chitinase
    Andrea M Olland
    Department of Chemical and Screening Sciences, Structural Biology and Computational Chemistry, Wyeth Research, Cambridge, Massachusetts 02140, USA
    Protein Sci 18:569-78. 2009
    ..As a novel target for asthma therapy, structural details of AMCase activity will help guide the future design of specific and potent AMCase inhibitors...
  13. doi Swift residue-screening identifies key N-glycosylated asparagines sufficient for surface expression of neuroglycoprotein Lingo-1
    Xiaotian Zhong
    Department of Chemical and Screening Sciences, Wyeth Research, 200 Cambridge Park Drive, Cambridge, MA 02140, USA
    FEBS Lett 583:1034-8. 2009
    ..The swift residue-screening approach may provide a new strategy for structural and functional analysis...
  14. pmc Engineering a monomeric Fc domain modality by N-glycosylation for the half-life extension of biotherapeutics
    Tetsuya Ishino
    Global Biotherapeutics Technologies, Pfizer Inc, Cambridge, Massachusetts 02140, USA
    J Biol Chem 288:16529-37. 2013
    ..This monoFc modality can be used to improve the pharmacokinetics of monomeric therapeutic proteins with an option to modulate the degree of half-life extension...
  15. pmc Expression, purification and crystallization of the ecto-enzymatic domain of rat E-NTPDase1 CD39
    Xiaotian Zhong
    Department of Chemical and Screening Sciences, Wyeth Research, 200 Cambridge Park Drive, Cambridge, MA 02140, USA
    Acta Crystallogr Sect F Struct Biol Cryst Commun 64:1063-5. 2008
    ..2 A data set using a maximum-likelihood molecular-replacement method as implemented in Phaser. The initial model of the two sCD39 monomers was placed into the P3(2) lattice and rigid-body refined and position-minimized with PHENIX...
  16. ncbi Catalytically active MAP KAP kinase 2 structures in complex with staurosporine and ADP reveal differences with the autoinhibited enzyme
    Kathryn W Underwood
    Department of Biological Chemistry, Wyeth Research, 87 Cambridge Park Drive, Cambridge, MA 02140, USA
    Structure 11:627-36. 2003
    ..However, phosphorylation of MK2 41-364 by p38 restores the V(max) and K(m) for peptide substrate to values comparable to those seen in p38-activated MK2 41-400, suggesting a mechanism for regulation of enzyme activity...
  17. doi Engineering novel Lec1 glycosylation mutants in CHO-DUKX cells: molecular insights and effector modulation of N-acetylglucosaminyltransferase I
    Xiaotian Zhong
    Global Biotherapeutics Technologies, Pfizer Biotherapeutic Research and Development, 87 Cambridge Park Drive, Cambridge, Massachusetts 02140, USA
    Biotechnol Bioeng 109:1723-34. 2012
    ..The data support the hypothesis that modulating GnTI activity can influence antibody effector functions for proteins with an IgG1 immunoglobulin Fc domain...
  18. ncbi Crystal structure of the GpIbalpha-thrombin complex essential for platelet aggregation
    John J Dumas
    Department of Chemical and Screening Sciences, Wyeth, 200 Cambridge Park Drive, Cambridge, MA 02140, USA
    Science 301:222-6. 2003
    ..The details of these interactions reconcile GpIbalpha-thrombin binding modes that are presently controversial,highlighting two distinct interfaces that are potential targets for development of novel antithrombotic drugs...
  19. ncbi Development of a fluorescence polarization assay to screen for inhibitors of the FtsZ/ZipA interaction
    Cynthia Hess Kenny
    Screening Sciences, Biophysics Enzymology, Wyeth Research, Pearl River, NY 10965, USA
    Anal Biochem 323:224-33. 2003
    ..An X-ray costructure of a promising small molecule in this library complexed with ZipA(185-328) (KI=12 microM) revealed that the compound binds to the same hydrophobic pocket as the FtsZ(367-383) peptide...
  20. pmc Atypical antigen recognition mode of a shark immunoglobulin new antigen receptor (IgNAR) variable domain characterized by humanization and structural analysis
    Oleg V Kovalenko
    Global Biotherapeutics Technologies, Pfizer Research and Development, Cambridge, Massachusetts 02140, USA
    J Biol Chem 288:17408-19. 2013
    ..This information broadens the general understanding of antigen recognition and provides a framework for further design and humanization of shark IgNARs...
  21. doi 3,4-Dihydropyrimido(1,2-a)indol-10(2H)-ones as potent non-peptidic inhibitors of caspase-3
    Lisa M Havran
    Chemical Sciences, Wyeth Research, CN 8000, Princeton, NJ 08543, USA
    Bioorg Med Chem 17:7755-68. 2009
    ..The synthesis, biological evaluation and structure-activity relationships of the pyrimidoindolones are described...
  22. pmc Identification of the lateral interaction surfaces of human histocompatibility leukocyte antigen (HLA)-DM with HLA-DR1 by formation of tethered complexes that present enhanced HLA-DM catalysis
    Efstratios Stratikos
    Department of Cellular and Molecular Biology, Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA
    J Exp Med 196:173-83. 2002
    ....