Tilman M Hackeng

Summary

Affiliation: Maastricht University
Country: The Netherlands

Publications

  1. pmc Conformational changes in activated protein C caused by binding of the first epidermal growth factor-like module of protein S
    T M Hackeng
    Departments of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
    Biochem J 349:757-64. 2000
  2. pmc Chemical synthesis and spontaneous folding of a multidomain protein: anticoagulant microprotein S
    T M Hackeng
    Department of Molecular and Experimental Medicine, Skaggs Institute for Chemical Biology, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 97:14074-8. 2000
  3. pmc Total chemical synthesis of human matrix Gla protein
    T M Hackeng
    Department of Biochemistry, Cardiovascular Research Institute Maastricht, University Maastricht, The Netherlands
    Protein Sci 10:864-70. 2001
  4. doi request reprint Regulation of TFPI function by protein S
    T M Hackeng
    Department of Biochemistry, Cardiovascular Research Institute Maastricht CARIM, Maastricht University, Maastricht, The Netherlands
    J Thromb Haemost 7:165-8. 2009
  5. pmc Protein S stimulates inhibition of the tissue factor pathway by tissue factor pathway inhibitor
    Tilman M Hackeng
    Department of Biochemistry, Cardiovascular Research Institute Maastricht, University of Maastricht, The Netherlands
    Proc Natl Acad Sci U S A 103:3106-11. 2006
  6. ncbi request reprint Effect of oral contraceptives on the anticoagulant activity of protein S in plasma
    Rory R Koenen
    Department of Biochemistry, Cardiovascular Research Institute Maastricht, The Netherlands
    Thromb Haemost 93:853-9. 2005
  7. doi request reprint Incorporation of disulfide containing protein modules into multivalent antigenic conjugates: generation of antibodies against the thrombin-sensitive region of murine protein S
    Pieter Van de Vijver
    Department of Biochemistry, Maastricht University, Maastricht, The Netherlands
    J Am Chem Soc 134:19318-21. 2012
  8. doi request reprint The Kunitz 1 and Kunitz 3 domains of tissue factor pathway inhibitor are required for efficient inhibition of factor Xa
    Sameera Peraramelli
    Department of Biochemistry, Cardiovascular Research Institute Maastricht, University Maastricht, The Netherlands
    Thromb Haemost 108:266-76. 2012
  9. ncbi request reprint Inhibition of thrombin generation by protein S at low procoagulant stimuli: implications for maintenance of the hemostatic balance
    Kristin M Seré
    Department of Biochemistry, Cardiovascular Research Institute Maastricht, University Maastricht, 6200 MD Maastricht, The Netherlands
    Blood 104:3624-30. 2004
  10. pmc Genetic and pharmacological modifications of thrombin formation in apolipoprotein e-deficient mice determine atherosclerosis severity and atherothrombosis onset in a neutrophil-dependent manner
    Julian I Borissoff
    Laboratory for Clinical Thrombosis and Hemostasis, Department of Internal Medicine, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands
    PLoS ONE 8:e55784. 2013

Collaborators

Detail Information

Publications48

  1. pmc Conformational changes in activated protein C caused by binding of the first epidermal growth factor-like module of protein S
    T M Hackeng
    Departments of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
    Biochem J 349:757-64. 2000
    ..Thus we provide direct evidence for binding of protein S-EGF1 to APC and show that it induces a conformational change in APC...
  2. pmc Chemical synthesis and spontaneous folding of a multidomain protein: anticoagulant microprotein S
    T M Hackeng
    Department of Molecular and Experimental Medicine, Skaggs Institute for Chemical Biology, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 97:14074-8. 2000
    ..These results demonstrate that total chemical synthesis of proteins offers an effective way to generate multidomain biologically active proteins...
  3. pmc Total chemical synthesis of human matrix Gla protein
    T M Hackeng
    Department of Biochemistry, Cardiovascular Research Institute Maastricht, University Maastricht, The Netherlands
    Protein Sci 10:864-70. 2001
    ..In conclusion, facile and efficient chemical synthesis in combination with native chemical ligation yielded MGP preparations that can aid in unraveling the mechanism by which MGP prevents vascular calcification...
  4. doi request reprint Regulation of TFPI function by protein S
    T M Hackeng
    Department of Biochemistry, Cardiovascular Research Institute Maastricht CARIM, Maastricht University, Maastricht, The Netherlands
    J Thromb Haemost 7:165-8. 2009
    ....
  5. pmc Protein S stimulates inhibition of the tissue factor pathway by tissue factor pathway inhibitor
    Tilman M Hackeng
    Department of Biochemistry, Cardiovascular Research Institute Maastricht, University of Maastricht, The Netherlands
    Proc Natl Acad Sci U S A 103:3106-11. 2006
    ..Our data suggest that protein S deficiency not only increases the risk of thrombosis by impairing the protein C system but also by reducing the ability of TFPI to down-regulate the extrinsic coagulation pathway...
  6. ncbi request reprint Effect of oral contraceptives on the anticoagulant activity of protein S in plasma
    Rory R Koenen
    Department of Biochemistry, Cardiovascular Research Institute Maastricht, The Netherlands
    Thromb Haemost 93:853-9. 2005
    ..Functional impairment of protein S as a result of hormonal influence may, at least in part, contribute to the thrombotic risk of OC users...
  7. doi request reprint Incorporation of disulfide containing protein modules into multivalent antigenic conjugates: generation of antibodies against the thrombin-sensitive region of murine protein S
    Pieter Van de Vijver
    Department of Biochemistry, Maastricht University, Maastricht, The Netherlands
    J Am Chem Soc 134:19318-21. 2012
    ..This method was used to prepare multiple antigenic peptide constructs of the thrombin-sensitive loop region of murine anticoagulant protein S...
  8. doi request reprint The Kunitz 1 and Kunitz 3 domains of tissue factor pathway inhibitor are required for efficient inhibition of factor Xa
    Sameera Peraramelli
    Department of Biochemistry, Cardiovascular Research Institute Maastricht, University Maastricht, The Netherlands
    Thromb Haemost 108:266-76. 2012
    ..This inhibitory activity is counteracted by K3 and C-terminus...
  9. ncbi request reprint Inhibition of thrombin generation by protein S at low procoagulant stimuli: implications for maintenance of the hemostatic balance
    Kristin M Seré
    Department of Biochemistry, Cardiovascular Research Institute Maastricht, University Maastricht, 6200 MD Maastricht, The Netherlands
    Blood 104:3624-30. 2004
    ....
  10. pmc Genetic and pharmacological modifications of thrombin formation in apolipoprotein e-deficient mice determine atherosclerosis severity and atherothrombosis onset in a neutrophil-dependent manner
    Julian I Borissoff
    Laboratory for Clinical Thrombosis and Hemostasis, Department of Internal Medicine, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands
    PLoS ONE 8:e55784. 2013
    ....
  11. ncbi request reprint The Ser460Pro mutation in recombinant protein S Heerlen does not affect its APC-cofactor and APC-independent anticoagulant activities
    Rory R Koenen
    Department of Biochemistry, Cardiovascular Research Institute Maastricht, University Maastricht, The Netherlands
    Thromb Haemost 91:1105-14. 2004
    ....
  12. doi request reprint Molecular MRI of early thrombus formation using a bimodal alpha2-antiplasmin-based contrast agent
    Robbert Jan J H M Miserus
    Department of Radiology, Maastricht University Medical Centre, Maastricht, The Netherlands
    JACC Cardiovasc Imaging 2:987-96. 2009
    ..We aimed to investigate whether early thrombus formation can be visualized with in vivo magnetic resonance imaging (MRI) by the use of a novel bimodal alpha(2)-antiplasmin-based contrast agent (CA)...
  13. doi request reprint Protein S as cofactor for TFPI
    Tilman M Hackeng
    Department of Biochemistry, Cardiovascular Research Institute Maastricht, University Maastricht, Maastricht, The Netherlands
    Arterioscler Thromb Vasc Biol 29:2015-20. 2009
    ..The current review describes the background of the TFPI-cofactor activity of protein S as well as the rationale for the observation that the TFPI/protein S system particularly inhibits the TF pathway at low procoagulant stimuli...
  14. doi request reprint Gadolinium-labeled quantum dots for molecular magnetic resonance imaging: R1 versus R2 mapping
    Marlies Oostendorp
    Department of Radiology, Maastricht University Medical Centre MUMC, Maastricht, The Netherlands
    Magn Reson Med 64:291-8. 2010
    ..At a field strength of 7 T, longitudinal relaxation rate-based measures were superior to transverse relaxation rate-based measures in detecting both the level and spatial extent of contrast agent-induced relaxation rate changes...
  15. pmc The thrombin-sensitive region of protein S mediates phospholipid-dependent interaction with factor Xa
    Subramanian Yegneswaran
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 283:33046-52. 2008
    ..In controls, the TSR domain did not alter the anisotropy of DEGR-fIXa(i) and DEGR-fVIIa(i), respectively. These data demonstrate that membrane-bound fXa binding to protein S involves the TSR of protein S...
  16. doi request reprint Early atherosclerosis exhibits an enhanced procoagulant state
    Julian Ilcheff Borissoff
    Laboratory for Clinical Thrombosis and Hemostasis, Department of Internal Medicine, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Universiteitsingel 50, PO Box 616, Box 8, 6200 MD Maastricht, The Netherlands
    Circulation 122:821-30. 2010
    ..In the present study, we examined for the first time the activity and presence of relevant coagulation proteins in relation to the progression of atherosclerosis...
  17. doi request reprint TFPI-dependent activities of protein S
    Sameera Peraramelli
    Department of Biochemistry, Cardiovascular Research Institute Maastricht CARIM, University Maastricht, The Netherlands
    Thromb Res 129:S23-6. 2012
    ....
  18. ncbi request reprint Re-evaluation of the role of the protein S-C4b binding protein complex in activated protein C-catalyzed factor Va-inactivation
    Lisbeth F A Maurissen
    Department of Biochemistry, Cardiovascular Research Institute Maastricht, University Maastricht, Maastricht, The Netherlands
    Blood 111:3034-41. 2008
    ..These results are of interest for carriers of the factor V(Leiden) mutation (R(506)Q), as protein S-C4BP effectively enhances APC-catalyzed factor Va (R(306)) inactivation in plasma containing factor V(Leiden)...
  19. doi request reprint Plaque-associated vasa vasorum in aged apolipoprotein E-deficient mice exhibit proatherogenic functional features in vivo
    Timo Rademakers
    Maastricht University, P Debyelaan 25, Maastricht, 6229HX, The Netherlands
    Arterioscler Thromb Vasc Biol 33:249-56. 2013
    ..Here, we aimed to elucidate functional and morphological properties of plaque microvessels in mice in vivo...
  20. doi request reprint Pharmacokinetics of contrast agents targeted to the tumor vasculature in molecular magnetic resonance imaging
    Marlies Oostendorp
    Department of Radiology, Maastricht University Medical Centre MUMC, Maastricht, The Netherlands
    Contrast Media Mol Imaging 5:9-17. 2010
    ..Summarizing, molecular DCE-MRI with pharmacokinetic modeling provides unique information on contrast agent delivery and angiogenic activity in tumors...
  21. ncbi request reprint Protein S multimers are generated in vitro and affect protein S structure-function analyses
    Kristin M Seré
    Department of Biochemistry, Cardiovascular Research Institute Maastricht, University Maastricht, The Netherlands
    Semin Hematol 43:S111-20. 2006
    ....
  22. doi request reprint The role of tissue factor pathway inhibitor in atherosclerosis and arterial thrombosis
    Kristien Winckers
    Department of Biochemistry, Cardiovascular Research Institute Maastricht, MUMC, Maastricht, The Netherlands
    Blood Rev 27:119-32. 2013
    ..The current review focuses on TFPI in clinical studies of asymptomatic and symptomatic atherosclerosis, coronary artery disease and ischemic stroke, and discusses potential atheroprotective actions of TFPI...
  23. pmc Similar hypercoagulable state and thrombosis risk in type I and type III protein S-deficient individuals from families with mixed type I/III protein S deficiency
    Elisabetta Castoldi
    Department of Biochemistry, Maastricht University P O Box 616, 6200 Maastricht, The Netherlands
    Haematologica 95:1563-71. 2010
    ....
  24. ncbi request reprint The APC-independent anticoagulant activity of protein S in plasma is decreased by elevated prothrombin levels due to the prothrombin G20210A mutation
    Rory R Koenen
    Department of Biochemistry, Cardiovascular Research Institute Maastricht, University Maastricht, 6200 MD Maastricht, The Netherlands
    Blood 102:1686-92. 2003
    ..47 +/- 0.21; n = 46). We propose that the decreased APC-independent anticoagulant activity of protein S in plasma with elevated prothrombin levels may contribute to the thrombotic risk associated with the prothrombin G20210A mutation...
  25. doi request reprint Nanoparticles for optical molecular imaging of atherosclerosis
    Kim Douma
    Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
    Small 5:544-57. 2009
    ..In this review, we provide an overview of both current optical nanoparticles and targeting ligands for optical molecular imaging of atherosclerotic lesions and speculate on their applicability in the clinical setting...
  26. doi request reprint Endothelial junctional adhesion molecule-a guides monocytes into flow-dependent predilection sites of atherosclerosis
    Martin M N Schmitt
    Institute for Cardiovascular Prevention, Ludwig Maximilians University Munich, Munich, Germany M M N S, R T A M, K B, R R K, C W the Institute for Molecular Cardiovascular Research, RWTH Aachen University, Aachen, Germany M M N S, M A v Z the Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands M M N S, R T A M, N M v d A, T R, M A v Z, T M H, R R K, C W the Division of Vascular Biology, Department of Vascular Surgery, Klinikum rechts der Isar, Technical University Munich, Germany A Z and the German Centre for Cardiovascular Research DZHK, partner site Munich Heart Alliance, Munich, Germany A Z, C W
    Circulation 129:66-76. 2014
    ..Atherosclerosis develops at sites of disturbed flow in large arteries, but the mechanisms guiding inflammatory cells into these predilection sites remain unknown...
  27. doi request reprint Chemoselective oxime reactions in proteins and peptides by using an optimized oxime strategy: the demise of levulinic Acid
    Stijn M Agten
    Department of Biochemistry, Cardiovascular Research Institute Maastricht CARIM, Maastricht University, P O Box 616, 6200 MD Maastricht The Netherlands
    Chembiochem 14:2431-4. 2013
    ..A mechanism for cyclization is proposed and alternative keto-acids have been tested. These showed faster formation of oximes without side products. ..
  28. doi request reprint Antisense-based RNA therapy of factor V deficiency: in vitro and ex vivo rescue of a F5 deep-intronic splicing mutation
    Francesca Nuzzo
    Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
    Blood 122:3825-31. 2013
    ..Our data provide in vitro and ex vivo proof of principle for the efficacy of RNA therapy in severe FV deficiency, but additional cytotoxicity studies are warranted. ..
  29. ncbi request reprint Basic mechanisms of hemostasis
    Kristin M Seré
    Department of Biochemistry, Cardiovascular Research Institute Maastricht, University Maastricht, Maastricht, The Netherlands
    Semin Vasc Med 3:3-12. 2003
    ..Unfortunately, pathological disturbances can occur as a result of inherited or acquired coagulation factor deficiencies that may lead to bleeding or thrombotic disorders...
  30. doi request reprint Regulation of coagulation by protein S
    Elisabetta Castoldi
    Department of Biochemistry, Cardiovascular Research Institute Maastricht CARIM, Maastricht University, Maastricht, The Netherlands
    Curr Opin Hematol 15:529-36. 2008
    ..In this review, the regulation of thrombin generation by protein S and the pathophysiological implications of protein S deficiency are discussed in the light of recent findings on the anticoagulant function(s) of protein S...
  31. doi request reprint Clinical perspectives of hybrid proton-fluorine magnetic resonance imaging and spectroscopy
    Martijn Wolters
    Department of Radiology, Maastricht University Medical Center, Maastricht, The Netherlands
    Invest Radiol 48:341-50. 2013
    ..This review outlines the translation from recent advances in preclinical MR imaging and spectroscopy to future perspectives of clinical hybrid 1H/19/F MR imaging applications...
  32. doi request reprint Vascular calcification: the price to pay for anticoagulation therapy with vitamin K-antagonists
    Martijn L L Chatrou
    Department of Biochemistry, Cardiovascular Research Institute Maastricht, MUMC, Maastricht, The Netherlands
    Blood Rev 26:155-66. 2012
    ..We conclude that there is a growing need for better understanding of the effects of anticoagulants on vascular calcification and atherosclerosis...
  33. doi request reprint Endothelin-1 and -2: two amino acids matter
    Matthijs G Compeer
    Department of Pharmacology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
    Life Sci 91:607-12. 2012
    ..We studied agonist-dependent aspects of endothelin(A) (ET(A))-receptor function and the importance of amino acids 6 and 7 of ET-1 and ET-2 in this respect...
  34. doi request reprint Blocking of frizzled signaling with a homologous peptide fragment of wnt3a/wnt5a reduces infarct expansion and prevents the development of heart failure after myocardial infarction
    Hilde Laeremans
    Department of Pharmacology and Toxicology, Cardiovascular Research Institute Maastricht, Maastricht University, 50 Universiteitssingel, 6229ER Maastricht PO Box 616, 6200MD Maastricht, Netherlands
    Circulation 124:1626-35. 2011
    ..In this study, we evaluated Frizzled as a novel therapeutic target for MI. These Frizzled proteins act as receptors for Wnt proteins and were previously shown to be expressed in the healing infarct...
  35. doi request reprint Nepsilon-(thiaprolyl)-lysine as a handle for site-specific protein conjugation
    Pieter Van de Vijver
    Department of Biochemistry, Cardiovascular Research Institute Maastricht, University Maastricht, The Netherlands
    Biopolymers 94:465-74. 2010
    ..This side chain protection strategy enables the use of readily available thiol-reactive probes for the modification of internally disulfide bonded proteins...
  36. doi request reprint Synthesis and application of cNGR-containing imaging agents for detection of angiogenesis
    Ingrid Dijkgraaf
    Department of Biochemistry, Cardiovascular Research Institute Maastricht CARIM, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands
    Bioorg Med Chem 21:3555-64. 2013
    ..Here, an overview on the currently used CD13 targeted molecular imaging probes for noninvasive visualization of angiogenesis is given...
  37. doi request reprint A positive family history for premature cardiovascular disease identifies patients prone to recurrent arterial thrombotic events
    Ties A Mulders
    University Medical Centre, Maastricht, The Netherlands
    Eur J Prev Cardiol 19:1465-73. 2012
    ..Whether either of these presentations is more likely in patients with a genetic predisposition for CVD is still unknown. We suggest that a genetic predisposition for CVD is related to recurrent events of the same nature...
  38. doi request reprint The circulating inactive form of matrix Gla Protein (ucMGP) as a biomarker for cardiovascular calcification
    Ellen C M Cranenburg
    VitaK, Maastricht University, Maastricht, The Netherlands
    J Vasc Res 45:427-36. 2008
    ..Here we report on the development of an ucMGP assay and the potential diagnostic utility of monitoring serum ucMGP levels...
  39. ncbi request reprint Optical and magnetic resonance imaging of cell death and platelet activation using annexin a5-functionalized quantum dots
    Lenneke Prinzen
    Department of Biophysics, University of Maastricht, and Department of Radiology, University Hospital Maastricht, The Netherlands
    Nano Lett 7:93-100. 2007
    ..The nanoparticle is suitable for both anatomic and subcellular imaging of structures in the vessel wall and is a promising bimodal contrast agent for future in vivo imaging studies...
  40. pmc Noninvasive diagnosis of ruptured peripheral atherosclerotic lesions and myocardial infarction by antibody profiling
    Kitty B J M Cleutjens
    Department of Pathology, Cardiovascular Research Institute Maastricht CARIM, University of Maastricht, Maastricht, The Netherlands
    J Clin Invest 118:2979-85. 2008
    ....
  41. pmc Plasma protein S residues 37-50 mediate its binding to factor Va and inhibition of blood coagulation
    Mary J Heeb
    Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037, USA
    Thromb Haemost 110:275-82. 2013
    ..These data implicate PS residues 37-50 as a binding site for FVa that mediates, at least in part, the direct inhibition of FVa-dependent procoagulant activity by PS. ..
  42. doi request reprint Application of an omonasteine ligation strategy for the total chemical synthesis of the BRD7 bromodomain
    Pieter Van de Vijver
    Laboratory for Chemical Protein Synthesis, Department of Biochemistry, Maastricht University, Universiteitssingel 50, 6200 MD, Maastricht, The Netherlands
    Chem Commun (Camb) 48:9403-5. 2012
    ..Hcy-to-Omo conversion can be performed on-resin, while the Omo-to-Hcy deprotection can be performed in situ after peptide ligation. This strategy was successfully applied in the synthesis of the BRD7 bromodomain...
  43. ncbi request reprint Nucleophilic catalysis of hydrazone formation and transimination: implications for dynamic covalent chemistry
    Anouk Dirksen
    Department of Cell Biology, Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Am Chem Soc 128:15602-3. 2006
    ..The strong enhancement in the rate of hydrazone equilibration broadens the scope of this stable imine in the field of dynamic covalent chemistry...
  44. pmc Stimuli of sensory-motor nerves terminate arterial contractile effects of endothelin-1 by CGRP and dissociation of ET-1/ET(A)-receptor complexes
    Merlijn J P M T Meens
    Department of Pharmacology and Toxicology, Cardiovascular Research Institute Maastricht CARIM, Maastricht University, Maastricht, The Netherlands
    PLoS ONE 5:e10917. 2010
    ..We tested whether the quasi-irreversible receptor-binding of ET-1 (i) limits reversing effects of the antagonists and (ii) can be selectively dissociated by an endogenous counterbalancing mechanism...
  45. ncbi request reprint cNGR: a novel homing sequence for CD13/APN targeted molecular imaging of murine cardiac angiogenesis in vivo
    Alexandra Buehler
    CARIM, University of Maastricht, Maastricht, The Netherlands
    Arterioscler Thromb Vasc Biol 26:2681-7. 2006
    ..Here, we investigated the feasibility of selective imaging of cardiac angiogenesis using the cNGR-CD13/APN system...
  46. ncbi request reprint A structural model of the SHBG domain of human variant protein S Heerlen
    Gerry A F Nicolaes
    Thromb Haemost 96:538-40. 2006
  47. ncbi request reprint Design and synthesis of a bimodal target-specific contrast agent for angiogenesis
    Anouk Dirksen
    Laboratory of Macromolecular and Organic Chemistry, Eindhoven University of Technology, P O Box 513, 5600 MB Eindhoven, The Netherlands
    Org Lett 6:4857-60. 2004
    ....
  48. ncbi request reprint In vivo clearance of human protein S in a mouse model: influence of C4b-binding protein and the Heerlen polymorphism
    Cecile V Denis
    INSERM U 143, Kremlin Bicetre, France
    Arterioscler Thromb Vasc Biol 25:2209-15. 2005
    ..To explore the effect of the Heerlen polymorphism and C4b-binding protein (C4BP) on protein S catabolism in vitro and in vivo...