intensity [64]. Conversely, peptide 10.3 presented better selectivity toward HDACs
6 and 10 [64]. This study further confirms the potential of hydroxamic acidcontaining peptides for studying HDAC function. The peptide sequence modulated
distinct enrichment profiles not only in terms of HDAC isotypes but also of the
interacting partners. Therefore, it would be interesting to profile several acetylation
sites and to investigate the differences in the recruitment of HDAC-containing
complexes. On the other hand, it remains to be seen whether Asuha-containing
peptides could provide information about the substrate selectivity of HDACs and
HDAC-containing complexes. A study employing nucleosomes with Asuhacontaining histone 3 (H3K9Asuha and H3K14Asuha) as inhibitors failed at
reproducing preferences in CoREST-mediated deacetylation [99]. Nevertheless,
further investigation would be needed in order to extract a definite conclusion.
6 Conclusions and Future Perspectives
Zn
2+ -dependent HDACs are involved in the epigenetic control of gene expression
and multiple other biological pathways. They draw special interest because of their
role in complex diseases such as autoimmune response and neurodegeneration, and
G N
H
Ac
O
G
C
NH 2
10.1, n = 1-4
H K
S R
N
H
O
O
N
H
OH
F K
L M
NH 2
10.2
T E
Ahx
C
G D
M
N
H
Ac
O
O
N
H
OH
W E
P I
NH 2
Q
Ahx
C
T
NH
O
OH
n
peg
10.3
Ac
Fig. 10 Chemical structures of hydroxamic acid-containing peptides used for the pulldown of
HDACs and their interacting partners from biological samples. Peg polyethylene glycol linker, Ahx
6-aminohexanoyl linker
Hydroxamic Acid-Containing Peptides in the Study of Histone Deacetylases
47
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