University of Groningen Chemistry-based enzyme detection ... · Thesis Marilena Ourailidou.indb 129 29-08-16 20:11. Processed on: 30-8-2016 504765-L-sub01-bw-Ourailidou Chapter 5

University of Groningen

Chemistry-based enzyme detection and inhibition in epigeneticsOurailidou, Maria-Eleni

IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.

Document VersionPublisher's PDF, also known as Version of record

Publication date:2016

Link to publication in University of Groningen/UMCG research database

Citation for published version (APA):Ourailidou, M-E. (2016). Chemistry-based enzyme detection and inhibition in epigenetics. [Groningen]:University of Groningen.

CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).

Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.

Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.

Download date: 03-09-2020

https://www.rug.nl/research/portal/en/publications/chemistrybased-enzyme-detection-and-inhibition-in-epigenetics(c6a7e757-c889-4542-ae9a-edcf719f7e1a).html

https://www.rug.nl/research/portal/en/publications/chemistrybased-enzyme-detection-and-inhibition-in-epigenetics(c6a7e757-c889-4542-ae9a-edcf719f7e1a).html

Processed on: 30-8-2016Processed on: 30-8-2016Processed on: 30-8-2016Processed on: 30-8-2016

504765-L-sub01-bw-Ourailidou504765-L-sub01-bw-Ourailidou504765-L-sub01-bw-Ourailidou504765-L-sub01-bw-Ourailidou

Thesis Marilena Ourailidou.indb 129 29-08-16 20:11



Chapter 5

130

5




Light-controlled HDAC inhibitors

131

5




Chapter 5

132

5+

Figure 1.





133

5

Figure 2.




Chapter 5

134

5

Figure 3. 1 12

1 12





135

5

1 7

1 23

4 5

6 27

8 12

89 10 11 9

10 118 9

12

1 3

4 51 2

1 3 4 5 7




Chapter 5

136

5

(

8 12

7

1 12

2 5

38 12

in vivo

1 2 3

237

3 1 2

76 2

5





137

5Figure 4.

8 12

8 12

8 12

3




Chapter 5

138

5

HD

AC1

HDAC

2

IC50

[μM

] HD

AC3

HD

AC6

HD

AC8

1 2 3 5 6 7 8 12





139

5

1 2

12

12

12

12

12

12

12




Chapter 5

140

5

12

Figure 5. 12

1212

12





141

5

12

7




Chapter 5

142

5





143

5




Chapter 5

144

5

o





145

5




Chapter 5

146

5

H2 2 H2 JH2 J H2 H3 J

H J H H

+

13

H2 2 H2 J H2 JH2 H2 H3 J

H J H H

+

14

H2 2H2 J H2 J H2

H3 H H J HJ H J H

+

trans-1: trans 1 8

15





147

5

H2 2 H2J H2 J H2

H H H HH

+

cis-1: cis 1 8

trans-1 cis-1

H2 2 H2 J H2 JH2 J H J H J

H J H J HH H H

H2 2 H2 JH2 J H2 H3 H2J H J H J

H H H

+

16




Chapter 5

148

5

H2 2H2 J H2 J H2 H3

H J HJ H J H H

+

trans-2: trans 1 8

17

t

H2 2 H2 J H2J H2 H J H J

H H H HH

+

cis-2: cis 1 8

trans-2cis-2

H2 2 H2 J H2 JH2 J H J H

H H H HH

o





149

5

J J J

18

H2 2H2 J H2 J

CH2 H3 J H JH H H J

H H

+

trans-3: trans- 1 8

19

H2 2 H2 H2J H2 J H2 J H

J H H JH J H J H H

H H

+

cis-3: trans- 1 8

trans-3cis-3

H2 2 H2 H2 JH2 J H2 J H

J H H J HJ H H H H




Chapter 5

150

5

14

H2 2 H2H2 H3 J H J

H H H

+

-ate 20

H2 2 H2 JCH2 J H2 H3 H3

J H H J HH

+

trans-4: trans 1 8 -21





151

5

H2 2H2 J H J

CH J H2 H3 J HH J H H

H H

+

cis-4: cis 1 8 -trans-4

cis-4H2 2 H2 J

H J H J H2H3 J H H

J H H H H

16

H2 2 H2 JH2 J H2 H3 J

H J H J H JH J H HH

+




Chapter 5

152

5

-te. 22

H2 2 H2 JH2 J H2 H3 H3

J H J H H JH J H J H

+

trans-5: trans 1 8 -23

H2 2 H2 JH2 J H2 H3 HJ H J H J

H J H J HH H

+

cis-5: cis 1 8 -trans-5

cis-5H2 2 H2 J H2

J H2 H3 J HH J H H J

H H H H





153

5

24: N

CH3 H H J HJ H H

24

H2 HH H H J H

25

JCH3 H2 H2 JCH2 J H2 J H2

H J H HH H

+

trans-6: trans 1 7

26




Chapter 5

154

5

H2 H2 J H2J H2 H J H

H H H HH

+

cis-6: trans- 1 7

trans-6cis-6

H2 H2 J H2 JH2 J H J HH H H H

J J JJ

+

27





155

5

H2 2 H2 H2 JCH2 J H2 H3 H3

H3 J H J HJ H J H +

trans-7: trans 1

8 28

H2 2 H2CH2 J H2 J H2CH3 H3 H3 J H

J H J H J HH H H

+

cis-7: cis 1 8-trans-7

cis-7H2 2 H2

H2 J H2 J H2CH3 H3 H3 J H

J H J H J HH H H




Chapter 5

156

5J H2 J

H2 H3 J H JH

29J H2 J

H2 H2 H3 J HJ H

29

J H2 J H2 H3 JH J H J H J

H H

+





157

5

30

J H2 JCH2 H3 H3 J HJ H J H J H

+

trans-8: trans-N -31

JH2 J H2 H3 J

H J H J H JH H H

+

cis-8: cis-Ntrans-8

cis-8 JH2 J H2 H3 J

H H J H HH

30

JH2 J H2 H3 H2

J H J H HJ H J H

+




Chapter 5

158

5

trans-9: trans-N -32

JH2 J H2 H2 J

H H J H JH H H

+

cis-9: trans-N -trans-9

cis-9J H2 J H2 H2

J H J H J HJ H H H

H





159

5

H3H2 J H J H J

H J H H

+

33

H2H3 H3 J H J

H J H J H

+

trans-10: trans N -34

H2 H2 JH J H J H J

H H

+

cis-10: cis Ntrans-10

cis-10H2 H3 J H

H J H

33




Chapter 5

160

5

H2 H3 H2J H H J HJ H

+

trans-11: trans N -35

H2 H2 J HH J H J H

H H

+

cis-11: cis Ntrans-11

cis-11H2 H2 J H J

H J H J HH H H





161

5

JCH3 J H2 J H J

J H JH J H

+

36

J H3 H3 JH2 J H J H

J H J H JH J H

+

trans-12: trans-N-

37

H3J H J H J

H J H J H JH H H

+

cis-12: cis-N- -de. trans-12

cis-12H3 J H H

J H J H HH




Chapter 5

162

5

Figure S1. 1-12





163

5

Figure S2. 1-12




Chapter 5

164

5

Figure S3.





165

5

Figure S4 1-12




Chapter 5

166

5

Figure S5. 1-12





167

5

Figure S6. 1212

t0.5 = 74 min

t0.5 = 4.25h

t0.5 = 67 min




Chapter 5

168

5

1 12





169

5




Chapter 5

170

5Figure S7.





171

5

Figure S8.




Chapter 5

172

5

7

2 7





173

5

Figure S9.




Chapter 5

174

5Figure S10.





175

5

trans-cis

12

12

Figure S11.




Chapter 5

176

5

Figure S12. 12





177

5Figure S13.

12

12

12

12




Chapter 5

178

5

In situ

12

Figure S14. 12 12





179

5

Figure S15.




Chapter 5

180

5Figure S16.

3





181

5

trans-cis

3

Figure S17. 3 3




Chapter 5

182

5

Figure S18.





183

5

Figure S19.




Chapter 5

184

5

Figure S20.

Figure S21.





185

5

Figure S22.




Chapter 5

186

5

7





187

5

Figure S23.




Chapter 5

188

5

trans and cis-12

1212

Figure S24.12





189

5

in vitro via




Chapter 5

190

5


Documents

University of Groningen Chemistry-based enzyme detection ... · Thesis Marilena Ourailidou.indb 129 29-08-16 20:11. Processed on: 30-8-2016 504765-L-sub01-bw-Ourailidou Chapter 5