Search

Your search keyword '"Agten, Stijn M"' showing total 25 results
Start Over Author "Agten, Stijn M"
25 results on '"Agten, Stijn M"'

2. Targeting platelet-derived CXCL12 impedes arterial thrombosis

Author

Leberzammer, Julian, Agten, Stijn M., Blanchet, Xavier, Duan, Rundan, Ippel, Hans, Megens, Remco T.A., Schulz, Christian, Aslani, Maria, Duchene, Johan, Döring, Yvonne, Jooss, Natalie J., Zhang, Pengyu, Brandl, Richard, Stark, Konstantin, Siess, Wolfgang, Jurk, Kerstin, Heemskerk, Johan W.M., Hackeng, Tilman M., Mayo, Kevin H., Weber, Christian, and von Hundelshausen, Philipp

Published
2022
Full Text
View/download PDF

5. Structure-Based Cyclic Glycoprotein Ibα-Derived Peptides Interfering with von Willebrand Factor-Binding, Affecting Platelet Aggregation under Shear

Author

Hrdinova, Johana, primary, Fernández, Delia I., additional, Ercig, Bogac, additional, Tullemans, Bibian M. E., additional, Suylen, Dennis P. L., additional, Agten, Stijn M., additional, Jurk, Kerstin, additional, Hackeng, Tilman M., additional, Vanhoorelbeke, Karen, additional, Voorberg, Jan, additional, Reutelingsperger, Chris P. M., additional, Wichapong, Kanin, additional, Heemskerk, Johan W. M., additional, and Nicolaes, Gerry A. F., additional

Published
2022
Full Text
View/download PDF

7. Potent Cyclic Peptide Inhibitors of FXIIa Discovered by mRNA Display with Genetic Code Reprogramming

Author

Ford, Daniel J, Ford, Daniel J, Duggan, Nisharnthi M, Fry, Sarah E, Ripoll-Rozada, Jorge, Agten, Stijn M, Liu, Wenyu, Corcilius, Leo, Hackeng, Tilman M, van Oerle, Rene, Spronk, Henri M H, Ashhurst, Anneliese S, Mini Sasi, Vishnu, Kaczmarski, Joe A, Jackson, Colin J, Pereira, Pedro José Barbosa, Passioura, Toby, Suga, Hiroaki, Payne, Richard J, Ford, Daniel J, Ford, Daniel J, Duggan, Nisharnthi M, Fry, Sarah E, Ripoll-Rozada, Jorge, Agten, Stijn M, Liu, Wenyu, Corcilius, Leo, Hackeng, Tilman M, van Oerle, Rene, Spronk, Henri M H, Ashhurst, Anneliese S, Mini Sasi, Vishnu, Kaczmarski, Joe A, Jackson, Colin J, Pereira, Pedro José Barbosa, Passioura, Toby, Suga, Hiroaki, and Payne, Richard J

Abstract

The contact system comprises a series of serine proteases that mediate procoagulant and proinflammatory activities via the intrinsic pathway of coagulation and the kallikrein-kinin system, respectively. Inhibition of Factor XIIa (FXIIa), an initiator of the contact system, has been demonstrated to lead to thrombo-protection and anti-inflammatory effects in animal models and serves as a potentially safer target for the development of antithrombotics. Herein, we describe the use of the Randomised Nonstandard Peptide Integrated Discovery (RaPID) mRNA display technology to identify a series of potent and selective cyclic peptide inhibitors of FXIIa. Cyclic peptides were evaluated in vitro, and three lead compounds exhibited significant prolongation of aPTT, a reduction in thrombin generation, and an inhibition of bradykinin formation. We also describe our efforts to identify the critical residues for binding FXIIa through alanine scanning, analogue generation, and via in silico methods to predict the binding mode of our lead cyclic peptide inhibitors.

Published
2021

8. Potent Cyclic Peptide Inhibitors of FXIIa Discovered by mRNA Display with Genetic Code Reprogramming

Author

Ford, Daniel J., primary, Duggan, Nisharnthi M., additional, Fry, Sarah E., additional, Ripoll-Rozada, Jorge, additional, Agten, Stijn M., additional, Liu, Wenyu, additional, Corcilius, Leo, additional, Hackeng, Tilman M., additional, van Oerle, Rene, additional, Spronk, Henri M. H., additional, Ashhurst, Anneliese S., additional, Mini Sasi, Vishnu, additional, Kaczmarski, Joe A., additional, Jackson, Colin J., additional, Pereira, Pedro José Barbosa, additional, Passioura, Toby, additional, Suga, Hiroaki, additional, and Payne, Richard J., additional

Published
2021
Full Text
View/download PDF

13. Chemokine interactome mapping enables tailored intervention in acute and chronic inflammation

Author

von Hundelshausen, Philipp, von Hundelshausen, Philipp, Agten, Stijn M., Eckardt, Veit, Blanchet, Xavier, Schmitt, Martin M., Ippel, Hans, Neideck, Carlos, Bidzhekov, Kiril, Leberzammer, Julian, Wichapong, Kanin, Faussner, Alexander, Drechsler, Maik, Grommes, Jochen, van Geffen, Johanna P., Li, He, Ortega-Gomez, Almudena, Megens, Remco T. A., Naumann, Ronald, Dijkgraaf, Ingrid, Nicolaes, Gerry A. F., Doering, Yvonne, Soehnlein, Oliver, Lutgens, Esther, Heemskerk, Johan W. M., Koenen, Rory R., Mayo, Kevin H., Hackeng, Tilman M., Weber, Christian, von Hundelshausen, Philipp, von Hundelshausen, Philipp, Agten, Stijn M., Eckardt, Veit, Blanchet, Xavier, Schmitt, Martin M., Ippel, Hans, Neideck, Carlos, Bidzhekov, Kiril, Leberzammer, Julian, Wichapong, Kanin, Faussner, Alexander, Drechsler, Maik, Grommes, Jochen, van Geffen, Johanna P., Li, He, Ortega-Gomez, Almudena, Megens, Remco T. A., Naumann, Ronald, Dijkgraaf, Ingrid, Nicolaes, Gerry A. F., Doering, Yvonne, Soehnlein, Oliver, Lutgens, Esther, Heemskerk, Johan W. M., Koenen, Rory R., Mayo, Kevin H., Hackeng, Tilman M., and Weber, Christian

Abstract

Chemokines orchestrate leukocyte trafficking and function in health and disease. Heterophilic interactions between chemokines in a given microenvironment may amplify, inhibit, or modulate their activity; however, a systematic evaluation of the chemokine interactome has not been performed. We used immunoligand blotting and surface plasmon resonance to obtain a comprehensive map of chemokine-chemokine interactions and to confirm their specificity. Structure-function analyses revealed that chemokine activity can be enhanced by CC-type heterodimers but inhibited by CXC-type heterodimers. Functional synergism was achieved through receptor heteromerization induced by CCL5-CCL17 or receptor retention at the cell surface via auxiliary proteoglycan binding of CCL5-CXCL4. In contrast, inhibitory activity relied on conformational changes (in CXCL12), affecting receptor signaling. Obligate CC-type heterodimers showed high efficacy and potency and drove acute lung injury and atherosclerosis, processes abrogated by specific CCL5-derived peptide inhibitors or knock-in of an interaction-deficient CXCL4 variant. Atheroprotective effects of CCL17 deficiency were phenocopied by a CCL5-derived peptide disrupting CCL5-CCL17 heterodimers, whereas a CCL5 alpha-helix peptide mimicked inhibitory effects on CXCL12-driven platelet aggregation. Thus, formation of specific chemokine heterodimers differentially dictates functional activity and can be exploited for therapeutic targeting.

Published
2017

14. Oxime conjugation in protein chemistry: from carbonyl incorporation to nucleophilic catalysis

Author

Agten, Stijn M., Dawson, Philip E., Hackeng, Tilman M., Biochemie, Promovendi CD, and RS: CARIM - R1.01 - Blood proteins & engineering

Subjects
nucleophilic catalysis, ketone, aniline, carbonyl, oxime, aldehyde
Abstract

Use of oxime forming reactions has become a widely applied strategy for peptide and protein bioconjugation. The efficiency of the reaction and robust stability of the oxime product has led to the development of a growing list of methods to introduce the required ketone or aldehyde functionality site specifically into proteins. Early methods focused on site-specific oxidation of an N-terminal serine or threonine and more recently transamination methods have been developed to convert a broader set of N-terminal amino acids into a ketone or aldehyde. More recently, site-specific modification of protein has been attained through engineering enzymes involved in posttranslational modifications in order to accommodate aldehyde-containing substrates. Similarly, a growing list of unnatural amino acids can be introduced through development of selective amino-acyl tRNA synthetase/tRNA pairs combined with codon reassignment. In the case of glycoproteins, glycans can be selectively modified chemically or enzymatically to introduce aldehyde functional groups. Finally, the total chemical synthesis of proteins complements these biological and chemoenzymatic approaches. Once introduced, the oxime ligation of these aldehyde and ketone groups can be catalyzed by aniline or a variety of aniline derivatives to tune the activity, pH preference, stability and solubility of the catalyst. European Peptide Society and

Published
2016

15. Detection of Localized Hepatocellular Amino Acid Kinetics by using Mass Spectrometry Imaging of Stable Isotopes

Author

Arts, Martijn, primary, Soons, Zita, additional, Ellis, Shane R., additional, Pierzchalski, Keely A., additional, Balluff, Benjamin, additional, Eijkel, Gert B., additional, Dubois, Ludwig J., additional, Lieuwes, Natasja G., additional, Agten, Stijn M., additional, Hackeng, Tilman M., additional, van Loon, Luc J. C., additional, Heeren, Ron M. A., additional, and Olde Damink, Steven W. M., additional

Published
2017
Full Text
View/download PDF

16. Chemokine interactome mapping enables tailored intervention in acute and chronic inflammation

Author

von Hundelshausen, Philipp, primary, Agten, Stijn M., additional, Eckardt, Veit, additional, Blanchet, Xavier, additional, Schmitt, Martin M., additional, Ippel, Hans, additional, Neideck, Carlos, additional, Bidzhekov, Kiril, additional, Leberzammer, Julian, additional, Wichapong, Kanin, additional, Faussner, Alexander, additional, Drechsler, Maik, additional, Grommes, Jochen, additional, van Geffen, Johanna P., additional, Li, He, additional, Ortega-Gomez, Almudena, additional, Megens, Remco T. A., additional, Naumann, Ronald, additional, Dijkgraaf, Ingrid, additional, Nicolaes, Gerry A. F., additional, Döring, Yvonne, additional, Soehnlein, Oliver, additional, Lutgens, Esther, additional, Heemskerk, Johan W. M., additional, Koenen, Rory R., additional, Mayo, Kevin H., additional, Hackeng, Tilman M., additional, and Weber, Christian, additional

Published
2017
Full Text
View/download PDF

21. Proline Primed Helix Length as a Modulator of the Nuclear Receptor–Coactivator Interaction

Author

Fuchs, Sascha, primary, Nguyen, Hoang D., additional, Phan, Trang T. P., additional, Burton, Matthew F., additional, Nieto, Lidia, additional, de Vries-van Leeuwen, Ingrid J., additional, Schmidt, Andrea, additional, Goodarzifard, Monireh, additional, Agten, Stijn M., additional, Rose, Rolf, additional, Ottmann, Christian, additional, Milroy, Lech-Gustav, additional, and Brunsveld, Luc, additional

Published
2013
Full Text
View/download PDF

23. Thiol-ene conjugation of VEGF peptide to electrospun scaffolds as potential application for angiogenesis

Author

Yao, Tianyu, Chen, Honglin, Wang, Rong, Rivero, Rebeca, Wang, Fengyu, Kessels, Lilian, Agten, Stijn M., Hackeng, Tilman M., Wolfs, Tim G.A.M., Fan, Daidi, Baker, Matthew B., and Moroni, Lorenzo

Abstract

Vascular endothelial growth factor (VEGF) plays a vital role in promoting attachment and proliferation of endothelial cells, and induces angiogenesis. In recent years, much research has been conducted on functionalization of tissue engineering scaffolds with VEGF or VEGF-mimetic peptide to promote angiogenesis. However, most chemical reactions are nonspecific and require organic solvents, which can compromise control over functionalization and alter peptide/protein activity. An attractive alternative is the fabrication of functionalizable electrospun fibers, which can overcome these hurdles. In this study, we used thiol-ene chemistry for the conjugation of a VEGF-mimetic peptide to the surface of poly (ε-caprolactone) (PCL) fibrous scaffolds with varying amounts of a functional PCL-diacrylate (PCL-DA) polymer. 30% PCL-DA was selected due to homogeneous fiber morphology. A VEGF-mimetic peptide was then immobilized on PCL-DA fibrous scaffolds by a light-initiated thiol-ene reaction. 7-Mercapto-4-methylcoumarin, RGD-FITC peptide and VEGF-TAMRA mimetic peptide were used to validate the thiol-ene reaction with fibrous scaffolds. Tensile strength and elastic modulus of 30% PCL-DA fibrous scaffolds were significantly increased after the reaction. Conjugation of 30% PCL-DA fibrous scaffolds with VEGF peptide increased the surface water wettability of the scaffolds. Patterned structures could be obtained after using a photomask on the fibrous film. Moreover, in vitrostudies indicated that scaffolds functionalized with the VEGF-mimetic peptide were able to induce phosphorylation of VEGF receptor and enhanced HUVECs survival, proliferation and adhesion. A chick chorioallantoic membrane (CAM) assay further indicated that the VEGF peptide functionalized scaffolds are able to promote angiogenesis in vivo. These results show that scaffold functionalization can be controlled via a simple polymer mixing approach, and that the functionalized VEGF peptide-scaffolds have potential for vascular tissue regeneration.

Published
2022
Full Text
View/download PDF

24. Strategies for Site-Specific Radiolabeling of Peptides and Proteins

Author

Dijkgraaf, Ingrid, Agten, Stijn M., Bauwens, Matthias, and Hackeng, Tilman M.

Subjects
Medical
Abstract

Although anatomical imaging modalities (X-ray, computed tomography (CT), magnetic resonance imaging (MRI)) still have a higher spatial resolution (0.1–1 mm) than molecular imaging modalities (single-photon emission computed tomography (SPECT), positron emission tomography (PET), optical imaging (OI)), the advantage of molecular imaging is that it can detect molecular and cellular changes at the onset of a disease before it leads to morphological tissue changes, which can be detected by anatomical imaging. During the last decades, noninvasive diagnostic imaging has encountered a rapid growth due to the development of dedicated imaging equipment for preclinical animal studies. In addition, the introduction of multimodality imaging (PET/CT, SPECT/CT, PET/MRI) which combines high-resolution conventional anatomical imaging with high sensitivity of tracer-based molecular imaging techniques has led to successful accomplishments in this exciting field. In this book chapter, we will focus on chemical synthesis techniques for site-specific incorporation of radionuclide chelators. Subsequently, radiolabeling based on complexation of a radionuclide with a chelator will be discussed, with focus on: diethylenetriaminepentaacetic acid (DTPA), 1,4,7,10-tetraazacyclododecane-tetraacetic acid (DOTA), 1,4,7-triazacyclononane-triacetic acid (NOTA), hexa-histidine (His-tag), and 6-hydrazinonicotinic acid (HYNIC) that allow the production of peptides labeled with 18F, 68Ga, 99mTc, and 111In – the currently most widely used isotopes.

Published
2022

25. Oxime conjugation in protein chemistry: from carbonyl incorporation to nucleophilic catalysis.

Author

Agten SM, Dawson PE, and Hackeng TM

Subjects
Aldehydes chemistry, Amino Acids chemistry, Catalysis, Ketones chemistry, Proteins chemistry, Oximes chemistry, Protein Biosynthesis, Protein Engineering methods, Proteins chemical synthesis
Abstract

Use of oxime forming reactions has become a widely applied strategy for peptide and protein bioconjugation. The efficiency of the reaction and robust stability of the oxime product has led to the development of a growing list of methods to introduce the required ketone or aldehyde functionality site specifically into proteins. Early methods focused on site-specific oxidation of an N-terminal serine or threonine and more recently transamination methods have been developed to convert a broader set of N-terminal amino acids into a ketone or aldehyde. More recently, site-specific modification of protein has been attained through engineering enzymes involved in posttranslational modifications in order to accommodate aldehyde-containing substrates. Similarly, a growing list of unnatural amino acids can be introduced through development of selective amino-acyl tRNA synthetase/tRNA pairs combined with codon reassignment. In the case of glycoproteins, glycans can be selectively modified chemically or enzymatically to introduce aldehyde functional groups. Finally, the total chemical synthesis of proteins complements these biological and chemoenzymatic approaches. Once introduced, the oxime ligation of these aldehyde and ketone groups can be catalyzed by aniline or a variety of aniline derivatives to tune the activity, pH preference, stability and solubility of the catalyst. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd., (Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.)

Published
2016
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results