Cover Page The handle

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Cover Page

The handle

http://hdl.handle.net/1887/136534

holds various files of this Leiden

University dissertation.

Author:

Hogervorst, T.P.

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Targeting of antigen

presenting cells with

mannosylated conjugates

PROEFSCHRIFT

ter verkrijging van

de graad van Doctor aan de Universiteit Leiden,

op gezag van Rector Magnificus prof.mr. C.J.J.M. Stolker,

volgens besluit van het College voor Promoties

te verdedigen op 17 maart 2020

klokke 13:45

door

Tim Petrus Hogervorst

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Promotiecommissie

Promotor

:

Dr. J.D.C. Codée

Copromotor :

Prof.dr. G.A. van der Marel

Overige leden :

Prof.dr. H.S. Overkleeft

Prof.dr. J. Brouwer

Prof. dr. Y. van Kooyk (Amsterdam UMC, Amsterdam)

Dr. D.V. Filippov

Dr. M. Verdoes (Radboud UMC, Nijmegen)

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“Een uurtje werk”

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i

List of Abbreviations

iii

Chapter 1

1 Targeting of antigen presenting cells with mannosylated conjugates

Chapter 2

21 Multivalent oligomannoside clusters to probe C-type lectin receptor binding

Chapter 3

63 Large scale synthesis of a conjugation ready 2-butoxy-8-oxo-adenine analog TLR7-ligand

Chapter 4

81

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ii

Chapter 5

111 Development of a C-mannoside functionalized lysine for the synthesis of acid-stable

mannosylated peptides

Chapter 6

145 Synthesis of glycosylated BTA-core monomers for the formation of dynamic self-assembling

supramolecular fibers

Chapter 7

177 Summary and future prospects

Nederlandse Samenvatting

187 List of Publications

193

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iii

Å _. Ångstrom

Ac _. acetyl

ACN _. acetonitrile

AIBN _. α,α′-azoisobutyronitrile

APC _. antigen-presenting cells

APT _. attached proton test

aq. _. aqueous

arom _. aromatic

AuNP _. gold nanoparticles

Bn _. benzyl Boc-ON . 2-( tert-butoxycarbonyloxyimino)-2-phenylacetonitrile Bu _. butyl Bz _. benzoyl

CAR _. chimeric antigen receptor

CD _. cluster of differentiation

CHO _. Chinese hamster ovary

CLR _. C-type lectin receptors

COSY _. correlation spectroscopy

Cq _. quarternary carbon

CRD _. carbohydrate recognition domain

CuAAC . copper(I)-catalyzed alkyne-azide cycloaddition δ _. chemical shift d _. coublet DAMP . danger/damage-associated molecular pattern DC _. dendritic cell DCM _. dichloromethane DC-SIGN .

DC-specific ICAM-3 grabbing non-integrin

DIPEA _. N,N-diisopropylethylamine

DMAP _. 4-(N,N-dimethylamino)pyridine

DMF _. dimethylformamide

DMSO _. dimethylsulfoxide

e.g. _. exempli gratia

EBV _. transfected B-cell line

ECD _. extracellular domain

ECM _. extracellular matrix

eq _. molar equivalents

ESI _. electrospray ionization

Et _. ethyl

et al. _. et alia 'and others'

EtOAc _. ethylacetate

FACS _. fluorescence-activated cell sorting

FRET _. Förster resonance energy transfer

g _. gram

Gal _. galactose

GalNAc _. N-acetyl galactosamine

Glu _. glucose

h _. hours

HA _. hyaluronic acid

HFIP _. 1,1,1,3,3,3-hexafluoroisopropanol

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iv

HPLC . high-performance liquid chromatography HRMS .

high resolution mass spectroscopy HSQC

.

heteronuclear single quantum coherence Hz _. hertz i.e. _. id est IL _. interleukin IR _. infrared J _. J-coupling LC-MS .

liquid chromatography mass-spectrometry LCP _. lipid-core-peptide m _. multiplet M _. molar Man _. mannose MBL _. mannose-binding lectin Me _. methyl

MGL _. macrophage galactose-type lectin

MHC _. major histocompatibility complex

min _. minute

Mmt _. monomethoxy trityl

moDC _. monocyte derived dendritic cell

MR _. mannose receptor MS _. molecular sieves MS _. mass-spectrometry NBS _. N-bromosuccinimide n.d. not determined N.D. not determined NHS _. N-hydroxysuccinimide NIS _. N-iodosuccinimide NLR _. NOD-like receptor

NMR _. nuclear magnetic resonance

NOD . nucleotide-binding oligomerization domain PAMP . pathogen-associated molecular pattern PE _. petroleum ether

PEG _. polyethylene glycol

Ph _. phenyl

PMB _. para-Methoxybenzyl

PRR _. pathogen recognizing receptor

q _. quartet

qnt. _. quantitative

RI _. refractive index

RIG-like _. retinoic acid inducible gene-I-like

RLRs

.

retinoic acid-inducible gene-I-like receptors

RP _. reverse phase

rt _. room temperature

s _. singlet

sat. _. saturated

SLP _. synthetic long peptide

SPPS _. solid-phase peptide synthesis

SPR _. surface plasmon resonance

STORM

.

stochastic optical reconstruction microscopy

TAAs _. tumor-associated antigens

t-Bu _. tert-butyl

TCR _. T cell receptor

TFA _. trifluoroacetic acid

TFE _. 2,2,2-trifluoroethanol Th _. T helper cell THPTA . tris(3hydroxypropyl -triazolylmethyl)amine TIS _. tri-isopropylsilane TLR _. Toll-Like Receptor TLR7 _. Toll-Like receptor-7 TMS _. trimethylsilyl TMSOTf . trimethylsilyl trifluoromethanesulfonate

Treg _. regulatory T cells

TTox _. tetanus toxoid

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