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L. Plougastel, O. Koniev, S. Specklin, E. Decuypere, C. Créminon et al., thin layer chromatography (TLC) was performed using plates cut from glass sheets (silica gel 60F-254 from Merck). Visualization was achieved by 254 or 365 nm UV light and by immersion in an ethanolic solution of cerium sulfate, and subsequent treatment with a heat gun. Materials: All reagents were obtained from commercial sources and used without further purifications

, Reaction times listed refer to "hold time" at the specified temperature. 1 Ha n d 13 C NMR spectra were recorded at 23°C on a Bruker 400 or 500 spectrometers. Recorded shifts are reported in parts per million (?)a n d calibrated using residual undeuterated solvent signals. Data are represented as follows: Chemical shift, mutiplicity (s = singlet

H. Analytical and . Method, HPLC experiments were performed on a Shimadzu system (Pump: model LC 20-AD, UV-detector: SPD 20-A, Autosampler: SIL 20-A)

. Hn-m-r(-m-e-o-h-;-m-h-z, 25 -3 . 4 0( m ,2 H ) ,2 . 6 9-2 . 8 9( m ,2 H ) ,2 . 0 2-2 . 1 8( m ,2 H ) 76 : 2,2',2",2" '-((4-Phenylbutane-1,2-diyl)bis(azanetriyl))tetraacetic acid C 18 H 24 N 2 O 8 -Mw = 396.4 g/mol 75 (1 eq., 63 mg, 0.384 mmol) was dissolved in H 2 O(0.5mL)andc hloroaceticacid(6.02 eq., 218 mg, 2.31 mmol) was added. A solution of NaOH (14.2 eq, ? (ppm) 7.05 -7.43 (m, 5H), 3.51 -3.68 (m, 1H), vol.3

, 1 mmol) was dissolved in DMF (53.8 mL) and 4-bromo-1-butene (1 eq., 1.54 mL, 15.1 mmol) was added. The reaction mixture was stirred at 60°C overnight, diluted with water (500 mL) and extracted with DCM (4x150 mL). The organic layer was then washed with brine, dried over MgSO 4 and evaporated under vacuum. The residue was purified by flash chromatography (Cyclohexane/EtOAc gradient

, HN M R( M e O H -d 4 ,4 0 0M H z ) : ? (ppm) 7.72 -7.92 (m, 4H), vol.5

. Ms-(esi, 4-Diazidobutyl)isoindoline-1,3-dione C 12 H 11 N 7 O 2 -Mw = 285.3 g/mol 80 (1 eq., 2.2 g, 10.9 mmol), NaN 3 (15 eq., 10.7 g, 163 mmol) and Mn(OAc) 3 · 2H 2 O (3 eq., 8.79 g, 32.8 mmol) were suspended in acetic acid (50 mL) and stirred at reflux whereupon the salts dissolved. The heating was continued until the solution lightened from dark brown to light yellow. The mixture was cooled to room temperature, diluted with water and extracted with DCM. The combined extracts were washed with brine, dried over MgSO 4 , and evaporated under vacuum. The residue was purified by flash chromatography (Cyclohexane/EtOAc gradient, vol.81

. Hn-m-r(-c-h-l-o-r-o-f-o-r-m--d,

, Hz, 2H), 3.28 -3.64 (m, 3H), 1.75 -2.04 (m, 2H) 13 CN M R( C h l o r o f o r m -d, vol.1, pp.0-1

. Ms-(esi,

. Hn-m-r(-d-m-s-o--d, , vol.6

, 58 (m, 4H), 7.22 (t, J =7 . 3H z ,0 . 2 5 H ) ,7 . 1 7( t ,J =7 . 3H z ,0 . 7 5 H ) ,3 . 8 7( s ,0 . 7 5 H ) , 3.83 (s, 2.25H) 13 CN M R( D M S O -d, vol.6

. Hn-m-r(-d-m-s-o--d, , vol.6

, 34 (s, 6H), Hz, 1H), 7.84 -8.06 (m, 5H), 7.61 -7.78 (m, 2H), vol.7

. Hz and . Cn-m-r(-d-m-s-o--d, , vol.6

, -oxo-1-phenyl-2,7,10-trioxa-4-azadodecan-12-yl)carbamoyl)phenyl)hydrazono)-2,3-dihydro-1H -inden-5-yl)-1H -1,2,3-triazol-1-yl)-3,6, MS (ESI, m/z): [M+H] + =5 8 3 107 : tert-Butyl-(E )-1, vol.9, pp.18-21

. Hn-m-r(-d-m-s-o--d-6, ? (ppm) 13.21 (br.s, 1H), 9.00 (d, J =4 . 5H z ,1 H ) , 8.58 (t, J =5.4Hz,1H),8.47(t,J =7.4Hz,1H),8.39(s,1H),7.97-8.11(m,3H)

. D-m-s-o--d, Hz, 2H), 1.43 (s, 9H) 13 CN M R, vol.6

. Ms-(esi,

, 18-hexaoxahenicosan-21-oyl)piperazine-1-104 mg, 0.27 mmol) and the amine 109a (52 mg, 0.14 mmol) using HATU as the coupling agent. The desired product was obtained as a colorless oil, vol.109, pp.4-7

. Hn-m-r(-d-m-s-o--d-6, ? (ppm) 12.59 (s, 1H), 8.26 (d, J =7 . 7H z ,1 H ) , 7.96 (d, J =7 . 9H z ,1 H ) ,7 . 8 9( t ,J =8 . 0H z ,1 H ) ,7 . 8 3( t d ,J =7 . 5 ,1 . 1H z ,1 H ) ,7 . 4 6-7.42 (m, 1H), 7.37 -7.35 (m, 1H), vol.7

, -Aminoethoxy)ethoxy)ethyl)-4-(2-(5-ethynyl-1,3-dioxo-1,3-dihydro-2H -inden-2-ylidene)1 eq., 70 mg, 0.12 mmol) was dissolved in TFA (2.2 mL) and thioanisole (50 eq., 0.711 mL, 6.01 mmol) was added. The reaction was stirred at rt overnight and concentrated under reduced pressure

. Hn-m-r(-m-e-o-h--d-4, ? (ppm) 7.88 -7.98 (m, 4H), 7.60 -7.75 (m, 3H), 4.01 (d, J =2 . 8H z ,1 H ) ,3 . 7 2( b r . s ,8 H ) ,3 . 5 7-3 . 6 5( m ,J =5 . 3H z ,2 H ) ,3 . 0 8-3 . 1 7 (m, 2H) 13 CN M R, vol.40

. Ms-(esi,

, -oxohexahydro-1H -thieno[3,41 eq., 7.5 mg, 0.017 mmol) and 112a (2 eq., 11.4 mg, 0.033 mmol) were dissolved in DMF (0.5 mL). DIPEA (10 eq., 0.0276 mL, 0.17 mmol) was added and the reaction mixture was stirred at rt overnight. The mixture was directly, vol.112

. Hn-m-r(-d-m-s-o--d, , vol.6

, Hz, 2H), 7.89 -8.01 (m, 5H), 7.82 (t, J =5 . 3H z ,2 H ) ,7 . 6 5-7 . 7 4( m ,2 H ), vol.6

, Hz, 2H), 1.41 -1.55 (m, 2H), 1.21 -1.29 (m, 2H)

, -oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)piperazin-1-yl)-21-oxo-3, MS (ESI, m/z): [M+H] + =6 7 5 108 : (E )-4, vol.6

. Hrms-(esi, , vol.57722, pp.tert-Butyl

, 222 mg, 0.593 mmol) in dry DMF (1 mL) was added 116 (1.2 eq., 300 mg, 0.712 mmol) and DIPEA (5.1 eq., 0.5 mL, 3.03 mmol). The mixture was stirred at rt for 3 h and then

. Hn-m-r-;-m-h-z,-m-e-o-h--,

;. Hz and . M-h-z,-m-e-o-h--, -Azidophenyl)-3-oxobutyl)-4-hydroxy-2H -chromen-2-one C 19 H 15 N 3 O 4 -Mw = 349.4 g/mol 128 (1 eq., 973 mg, 5.2 mmol) and 4-hydroxycoumarin (1.08 eq., 910 mg, 5.62 mmol) were dissolved in DCM (35 mL). S-proline (50 %, 299 mg, 2.6 mmol) was added and DMSO (15 mL) was added to solubilize it. The reaction mixture was stirred at rt overnight and DCM was removed under vacuum. The mixture was diluted with water (150 mL) and extracted with ethyl acetate (150 mL). The organic layer was washed with brine, 3.71 -3.56 (m, 8H),3.54(t,J=5.5Hz,2H),3.34(t,J=5.5Hz,2H),3.24-3.14(m,1H),2.92(dd,J =4.8,12.8Hz,1H),2.70(d,J=12.8Hz,1H),2.19(t,J=7.4Hz,2H),1.78-1.50(m, 4H ) ,1 . 4 8-1 . 3 5( m ,2H ) . 13 CN M R( 1 0 1, vol.122, p.3

. Hn-m-r-;-m-h-z, ? (ppm) 7.87 -7.95 (m, 1H), 7.62 -7.71 (m, 1H), 7.31 -7 . 4 4( m ,4 H ) ,7 . 0 3( d ,J =8 . 5H z ,1 . 4 H ), vol.6

. Hrms-(esi, ]triazol-1(4H )-yl)phenyl)-3-oxobutyl)-2H -chromen-2-one C 29 H 29 N 3 O 5 -Mw = 499.6 g/mol 122 (1 eq., 100 mg, 0.286 mmol) and BCN (4.65 eq., 200 mg, 1.33 mmol) were dissolved in DMSO (1 mL). The reaction was stirred at rt overnight and purified directly by preparative HPLC to give the desired compound (143 mg, 0.286 mmol, qtt) as a white powder, 6S,6aS )-6-(hydroxymethyl)-5,5a,6,6a, vol.129, p.8, 11358.

, HRMS (ESI,m/z) :c a l cf o rC 29 H 30 N 3 O 5, vol.500, 21800.

, Potassium Acetate, 20 mM Tris-acetate, 10 mM Magnesium Acetate, 1 mM DTT, 1 ng BSA. from Dr. Preudhomme (Laboratoire d'Hématologie du CHU de Lille), Biological Experimental Part Instrumentation Infra-red Imaging System : Li-Cor Odyssey Centrifugation : Centrifuge Br4i Jouan with S40 mobile rotor

, Cells were cultured in MEM? medium (InVitrogen) supplemented with 10 % FCS and 40 µg/ml 1 mM Sodium Orthovanadate. One complete EDTA-free protease inhibitor tablet (Roche) per 25 ml, 100 U of DNase I and 100 µgofRNaseApergramofcellw ere added. The sample was lysed by sonication (Bioblock scientific vibracell 72412, small probe, 35 % amplitude, 3 runs of 45s, 0.5s on/0150 mM NaCl, 2 mM MgCl2, 0.1 % Tween 20) with 20 nmol of probe Doxo-HAZA-biotine (10 mM) by incubation at rt for 1,5 h-2 h. 5 mg of cell extract was then applied on beads and incubated for 1 ha t4°C. After washes with purification buffer, proteins were eluted by adding 100 µlo f sodium dithionite 5 mM in purification buffer w/o Tween 20 at pH 7.2. For MS analysis, eluate was concentrated by speedvac and finally resuspended in sample buffer

/. Nanolc-nanoesi and . Ms-ms, analysis Mass spectrometry analyses were performed on an Orbitrap Elite instrument (Thermo Scientific) with nanoESI source interfaced to a nanoLC system (Ultimate 3000 RSLCnano System

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