The handle
http://hdl.handle.net/1887/87273
holds various files of this Leiden University
dissertation.
Author: Lahav, D.
125
List of Publications
A Fluorescence Polarization Activity-Based Protein Profiling Assay in the
Discovery of Potent, Selective Inhibitors for Human Nonlysosomal
Glucosylceramidase.
Lahav, D., Liu, B., van den Berg, R. J. B. H. N., van den Nieuwendijk, A. M. C. H.,
Wennekes, T., Ghisaidoobe, A. T., Breen, I., Ferraz, M. J., Kuo, C.-L., Wu, L., Geurink,
P. P., Ovaa, H., van der Marel, G. A., van der Stelt, M., Boot, R. G., Davies, G. J.,
Aerts, J. M. F. G., and Overkleeft, H. S. (2017) J. Am. Chem. Soc. 139, 14192–14197.
Lysosomal glycosphingolipid catabolism by acid ceramidase: formation of
glycosphingoid bases during deficiency of glycosidases.
Guimaraes Da Lomba Ferraz M.J., Marques A.R., Appelman M.D., Verhoek M.,
Strijland A., Mirzaian M., Scheij S., Ouairy C.M.J., Lahav D., Wisse P., Overkleeft
H.S., Boot R.G. and Aerts J.M.F.G. (2016) FEBS letters 590, 716-725.
Manno-Configured epi-Cyclophellitol Aziridine Based Fluorescence Polarization
Activity-Based Protein Profiling Identifies New Golgi α-Mannosidase Inhibitors.
Armstrong, Z., Lahav, D., Johnson, R., Kuo, C., Beenakker, T. J. M., de Boer, C.,
Wong, C. S., van Rijssel, E. R., Debets, M., Geurink, P. P., Ovaa, H., van der Stelt, M.,
Codée, J. D. C., Aerts, J. M. F. G., Wu, L., Overkleeft, H. S., Davies, G. J.
126
Curriculum Vitae
Nederlands
Daniël Lahav werd op 21 augustus 1987 geboren te Nahariya (Israël). Hij heeft
eerst zijn bachelor Chemie, met een minor in biochemie, cum laude behaald in
2012 aan de hogeschool in Rotterdam. Tijdens zijn bachelor heeft hij stage gelopen
op het Erasmus medisch centrum bij de afdelingen metabole ziekten van Dr. G.J.G.
Ruijter en genetica van Prof. Dr. R. Kanaar. Voor zijn afstudeerverslag heeft hij de
HAS-prijs behaald voor beste student verslag. Na zijn bachelor heeft hij zijn studie
voortgezet aan de Universiteit van Leiden waar hij in 2014 zijn master diploma
heeft behaald voor de onderzoeksmaster Design & Synthesis. In het kader van de
master opleiding heeft hij een onderzoeksstage verricht onder leiding van Prof. Dr.
M. van der Stelt in de vakgroep Bio-Organische Synthese van Prof. Dr. H.S.
Overkleeft. Dit onderzoek was gericht op het synthetiseren van een probe voor
GBA2 en hierbij een fluorescentie polarisatie assay op te zetten voor het screenen
van verbindingen als mogelijke remmers.
127
Curriculum Vitae
English
Daniël Lahav was born on 21
thof August 1987 in Nahariya (Israel). He obtained his
bachelor degree in Chemistry, with a minor in biochemistry, with distinctions in
2012 at the Hogeschool Rotterdam. During his bachelor he did research internships
at the Erasmus medical centre in the group of Dr. G.J.G. Ruijter and Prof. Dr. R.
Kanaar. For his report of the second internship, he received the HAS-price for best
student report. After his bachelor he continued his studies at Leiden University
where he obtained his chemistry research Master degree, with specialization
Design & Synthesis, in 2014. As part of the master program, he performed an
internship under supervision of Prof. Dr. M. van der Stelt in the workgroup
Bio-Organic Synthesis of Prof. Dr. H.S. Overkleeft. This research was aimed at
synthesising a probe for GBA2 and subsequently setting up a fluorescence
polarization assay to screen large compound libraries for hit identification.
January 2015 he started with his doctoral studies regarding the content of this
thesis in the group Bio-Organic Synthesis of Prof. Dr. H.S. Overkleeft. Posters of
parts of the PhD research were presented at several national conferences. An oral
presentation was given at the international Activity-based protein profiling and
biorthogonal chemistry conference in Leiden (2017).
128
APPENDIX
Chemical structures of the 358 compounds (with references) of which the
Leiden iminosugar library is composed and that have been used in the
FluoPol ABPP assays detailed in Chapters 2-5.
ID# Structure Ref
147
357 6
148
References
(1) Wennekes, T., Bonger, K. M., Vogel, K., van den Berg, R. J. B. H. N., Strijland, A., Donker-Koopman, W. E., Aerts, J. M. F. G., van der Marel, G. A., and Overkleeft, H. S. (2012) The development of an aza-C-glycoside library based on a tandem Staudinger/aza-Wittig/Ugi three-component reaction. Eur. J. Org. Chem. 2012, 6420–6454.
(2) Bonger, K. M., Wennekes, T., de Lavoir, S. V. P., Esposito, D., van den Berg, R. J. B. H. N., Litjens, R. E. J. N., van der Marel, G. A., and Overkleeft, H. S. (2006) Transformation of carbohydrate derived 4-azidopentanals into highly functionalized pyrrolidines via a tandem Staudinger/aza-Wittig/Ugi multicomponent reaction. QSAR Comb. Sci. 25, 491–503.
(3) Ghisaidoobe, A., Bikker, P., de Bruijn, A. C. J., Godschalk, F. D., Rogaar, E., Guijt, M. C., Hagens, P., Halma, J. M., van’t Hart, S. M., Luitjens, S. B., van Rixel, V. H. S., Wijzenbroek, M., Zweegers, T., Donker-Koopman, W. E., Strijland, A., Boot, R., van der Marel, G., Overkleeft, H. S., Aerts, J. M. F. G., and van den Berg, R. J. B. H. N. (2011) Identification of potent and selective glucosylceramide synthase inhibitors from a library of N-alkylated iminosugars. ACS Med. Chem. Lett. 2, 119–123. (4) van den Berg, R. J. B. H. N., Wennekes, T., Ghisaidoobe, A., Donker-Koopman, W.
E., Strijland, A., Boot, R. G., van der Marel, G. A., Aerts, J. M. F. G., and Overkleeft, H. S. (2011) Assessment of partially deoxygenated deoxynojirimycin derivatives as glucosylceramide synthase inhibitors. ACS Med. Chem. Lett. 2, 519–522.
(5) Lahav, D., Liu, B., van den Berg, R. J. B. H. N., van den Nieuwendijk, A. M. C. H., Wennekes, T., Ghisaidoobe, A. T., Breen, I., Ferraz, M. J., Kuo, C.-L., Wu, L., Geurink, P. P., Ovaa, H., van der Marel, G. A., van der Stelt, M., Boot, R. G., Davies, G. J., Aerts, J. M. F. G., and Overkleeft, H. S. (2017) A fluorescence polarization activity-based protein profiling assay in the discovery of potent, selective inhibitors for human nonlysosomal glucosylceramidase. J. Am. Chem. Soc. 139, 14192– 14197.
(6) Ghisaidoobe, A. T., van den Berg, R. J. B. H. N., Butt, S. S., Strijland, A., Donker-Koopman, W. E., Scheij, S., van den Nieuwendijk, A. M. C. H., Koomen, G.-J., van Loevezijn, A., Leemhuis, M., Wennekes, T., van der Stelt, M., van der Marel, G. A., van Boeckel, C. A. A., Aerts, J. M. F. G., and Overkleeft, H. S. (2014) Identification and development of biphenyl substituted iminosugars as improved dual glucosylceramide synthase/neutral glucosylceramidase inhibitors. J. Med. Chem.
57, 9096–9104.
(7) Wennekes, T., van den Berg, R. J. B. H. N., Boltje, T. J., Donker-Koopman, W. E., Kuijper, B., van der Marel, G. A., Strijland, A., Verhagen, C. P., Aerts, J. M. F. G., and Overkleeft, H. S. (2010) Synthesis and evaluation of lipophilic aza-C-glycosides as inhibitors of glucosylceramide metabolism. Eur. J. Org. Chem. 2010, 1258–1283. (8) Wennekes, T., Meijer, A. J., Groen, A. K., Boot, R. G., Groener, J. E., van Eijk, M.,
149
Copeland, D., van den Berg, R. J., van der Marel, G. A., Overkleeft, H. S., and Aerts, J. M. (2010) Dual-action lipophilic iminosugar improves glycemic control in obese rodents by reduction of visceral glycosphingolipids and buffering of carbohydrate assimilation. J. Med. Chem. 53, 689–698.
(9) Wennekes, T., van den Berg, R. J. B. H. N., Bonger, K. M., Donker-Koopman, W. E., Ghisaidoobe, A., van der Marel, G. A., Strijland, A., Aerts, J. M. F. G., and Overkleeft, H. S. (2009) Synthesis and evaluation of dimeric lipophilic iminosugars as inhibitors of glucosylceramide metabolism. Tetrahedron: Asymmetry 20, 836– 846.
(10) Overkleeft, H. S., Renkema, G. H., Neele, J., Vianello, P., Hung, I. O., Strijland, A., van der Burg, A. M., Koomen, G.-J., Pandit, U. K., and Aerts, J. M. F. G. (1998) Generation of specific deoxynojirimycin-type inhibitors of the non-lysosomal glucosylceramidase. J. Biol. Chem. 273, 26522–26527.
(11) Gloster, T. M., Roberts, S., Perugino, G., Rossi, M., Moracci, M., Panday, N., Terinek, M., Vasella, A., and Davies, G. J. (2006) Structural, kinetic, and thermodynamic analysis of glucoimidazole-derived glycosidase inhibitors.
Biochemistry 45, 11879–11884.
(12) Takahata, H., Banba, Y., Ouchi, H., and Nemoto, H. (2003) Concise and highly stereocontrolled synthesis of 1-deoxygalactonojirimycin and its congeners using dioxanylpiperidene, a promising chiral building block. Org. Lett. 5, 2527–2529. (13) Zhao, K., Zhou, G., Nie, H., and Chen, W. (2016) Three-step synthesis of
L-ido-1-deoxynojirimycin derivatives by reductive amination in water, “borrowing hydrogen” under neat conditions and deprotection. Org. Biomol. Chem. 14, 9466– 9471.
(14) Concia, A. L., Lozano, C., Castillo, J. A., Parella, T., Joglar, J., and Clapés, P. (2009) D-fructose-6-phosphate aldolase in organic synthesis: cascade chemical-enzymatic preparation of sugar-related polyhydroxylated compounds. Chemistry 15, 3808– 3816.
