potential for investigating HDAC function. Several examples of the application of
these chemotypes are discussed in this book chapter.
Keywords Cyclic peptide, Epigenetics, HDAC, Histone deacetylases, Hydroxamic
acid, Peptide probe
Abbreviations
Api
Apicidin
Asu
L-α-Aminosuberic acid
Asuha L-α-Aminosuberic hydroxamic acid
Azu
Azumamide
CHAP Cyclic hydroxamic acid-containing peptide
Chlam Chlamydocin
HCtx
HC-toxin
HDAC Histone deacetylase
Kac
ε-N-Acetyl-lysine
KDAC Lysine deacylase
NMR
Nuclear magnetic resonance
PTM
Posttranslational modification
SAHA Suberoylanilide hydroxamic acid
SAR
Structure-activity relationship
SPPS
Solid-phase peptide synthesis
Tpx
Trapoxin
TSA
Trichostatin A
1 Introduction
The first mammalian histone deacetylase (HDAC) was isolated and cloned in 1996
[1], identifying one of the key enzymes in Vincent Allfrey’s hypothesis that RNA
synthesis is regulated by reversible posttranslational histone modification
[2, 3]. Twenty years later, the superfamily of HDACs has been extensively
characterized and counts 18 proteins: 11 zinc-dependent enzymes divided into
classes I, II, and IV by sequence similarity [4] and 7 structurally distinct NAD
+
-
dependent enzymes known as the sirtuins [5].
The conventional enzymatic activity of these biomolecules is the removal of the
acetyl posttranslational modification (PTM) from ε-N-acetyllysine (Kac) residues.
Although the entire protein superfamily is referred to as “histone deacetylases,”
mainly class I members catalyze Kac hydrolysis at the tails of histone proteins
[6]. Thus, class I HDACs are present in the nucleus of human cells, where their
30
C. Moreno-Yruela and C. A. Olsen
these chemotypes are discussed in this book chapter.
Keywords Cyclic peptide, Epigenetics, HDAC, Histone deacetylases, Hydroxamic
acid, Peptide probe
Abbreviations
Api
Apicidin
Asu
L-α-Aminosuberic acid
Asuha L-α-Aminosuberic hydroxamic acid
Azu
Azumamide
CHAP Cyclic hydroxamic acid-containing peptide
Chlam Chlamydocin
HCtx
HC-toxin
HDAC Histone deacetylase
Kac
ε-N-Acetyl-lysine
KDAC Lysine deacylase
NMR
Nuclear magnetic resonance
PTM
Posttranslational modification
SAHA Suberoylanilide hydroxamic acid
SAR
Structure-activity relationship
SPPS
Solid-phase peptide synthesis
Tpx
Trapoxin
TSA
Trichostatin A
1 Introduction
The first mammalian histone deacetylase (HDAC) was isolated and cloned in 1996
[1], identifying one of the key enzymes in Vincent Allfrey’s hypothesis that RNA
synthesis is regulated by reversible posttranslational histone modification
[2, 3]. Twenty years later, the superfamily of HDACs has been extensively
characterized and counts 18 proteins: 11 zinc-dependent enzymes divided into
classes I, II, and IV by sequence similarity [4] and 7 structurally distinct NAD
+
-
dependent enzymes known as the sirtuins [5].
The conventional enzymatic activity of these biomolecules is the removal of the
acetyl posttranslational modification (PTM) from ε-N-acetyllysine (Kac) residues.
Although the entire protein superfamily is referred to as “histone deacetylases,”
mainly class I members catalyze Kac hydrolysis at the tails of histone proteins
[6]. Thus, class I HDACs are present in the nucleus of human cells, where their
30
C. Moreno-Yruela and C. A. Olsen