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Hydroxamic Acid-Containing Peptides in the Study of Histone Deacetylases

  • Carlos Moreno-Yruela
  • Christian A. OlsenEmail author
Chapter
Part of the Topics in Medicinal Chemistry book series

Abstract

Histone deacetylases (HDACs) are ubiquitous enzymes that remove ε-N-acetyl-lysine posttranslational modifications (PTMs) on histone tails. The resulting PTM landscape affects chromatin packing and recruitment of transcription factors, in turn playing an indirect role in regulation of gene expression. Deregulation of the activity of these hydrolases has been associated with several complex diseases. Thus, HDAC inhibitors have been approved for cancer treatment and are being studied against inflammation, neurodegeneration, and autoimmune disorders among others. The role of each of the 11 Zn2+-dependent HDACs has not yet been elucidated, mainly due to their structural similarity and, in part, due to the absence of isotype-selective probes. Such selectivity may be achievable by targeting features outside of the active site pocket, which is highly conserved. Peptides, which may cover larger areas than small molecules, may become useful chemical tools able to reach unexplored areas of the protein surface to achieve selectivity. In addition, by incorporating hydroxamic acid-containing lysine mimics in their structure, strong binding to the catalytic cavity is achieved. Furthermore, such molecules present similarities to the native substrates, which could be exploited for determining targets of their deacetylase activity. Therefore, hydroxamic acid-containing peptides have 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

Notes

Compliance with Ethical Standards

Funding: This work was supported by a Ph.D. fellowship funded by the University of Copenhagen.

Conflict of Interest: The authors declare no conflict of interest.

Ethical Approval: No part of the contents of this chapter requires ethical review.

Informed Consent: No part of the contents of this chapter requires informed consent.

References

  1. 1.
    Taunton J, Hassig CA, Schreiber SL (1996) A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p. Science 272(5260):408–410Google Scholar
  2. 2.
    Verdin E, Ott M (2015) 50 years of protein acetylation: from gene regulation to epigenetics, metabolism and beyond. Nat Rev Mol Cell Biol 16(4):258–264Google Scholar
  3. 3.
    Allfrey V, Faulkner R, Mirsky A (1964) Acetylation and methylation of histones and their possible role in the regulation of RNA synthesis. PNAS 51(5):786–794Google Scholar
  4. 4.
    Gregoretti IV, Lee Y-M, Goodson HV (2004) Molecular evolution of the histone deacetylase family: functional implications of phylogenetic analysis. J Mol Biol 338(1):17–31Google Scholar
  5. 5.
    Frye RA (2000) Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins. Biochem Biophys Res Commun 273(2):793–798Google Scholar
  6. 6.
    Yang X-J, Seto E (2008) The Rpd3/Hda1 family of lysine deacetylases: from bacteria and yeast to mice and men. Nat Rev Mol Cell Biol 9(3):206–218Google Scholar
  7. 7.
    Arrowsmith CH, Bountra C, Fish PV, Lee K, Schapira M (2012) Epigenetic protein families: a new frontier for drug discovery. Nat Rev Drug Discov 11(5):384–400Google Scholar
  8. 8.
    Millard CJ, Watson PJ, Fairall L, Schwabe JWR (2017) Targeting class I histone deacetylases in a “complex” environment. Trends Pharmacol Sci 38(4):363–377Google Scholar
  9. 9.
    Falkenberg KJ, Johnstone RW (2014) Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders. Nat Rev Drug Discov 13(9):673–691Google Scholar
  10. 10.
    Chakrabarti A, Oehme I, Witt O, Oliveira G, Sippl W, Romier C, Pierce RJ, Jung M (2015) HDAC8: a multifaceted target for therapeutic interventions. Trends Pharmacol Sci 36(7):481–492Google Scholar
  11. 11.
    Wei W, Liu X, Chen J, Gao S, Lu L, Zhang H, Ding G, Wang Z, Chen Z, Shi T, Li J, Yu J, Wong J (2017) Class I histone deacetylases are major histone decrotonylases: evidence for critical and broad function of histone crotonylation in transcription. Cell Res 27:898–915Google Scholar
  12. 12.
    Fellows R, Denizot J, Stellato C, Cuomo A, Jain P, Stoyanova E, Balázsi S, Hajnády Z, Liebert A, Kazakevych J, Blackburn H, Correa RO, Fachi JL, Sato FT, Ribeiro WR, Ferreira CM, Peree H, Spagnuolo M, Mattiuz R, Matolcsi C, Guedes J, Clark J, Veldhoen M, Bonaldi T, Ramirez Vinolo MA, Varga-Weisz P (2018) Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases. Nat Commun 9(105):1–15Google Scholar
  13. 13.
    Bradner JE, West N, Grachan ML, Greenberg EF, Haggarty SJ, Warnow T, Mazitschek R (2010) Chemical phylogenetics of histone deacetylases. Nat Chem Biol 6(3):238–243Google Scholar
  14. 14.
    Lahm A, Paolini C, Pallaoro M, Nardi M, Jones P, Neddermann P, Sambucini S, Bottomley M, Surdo PL, Carfı A, Koch U, De Francesco R, Seinkühler C, Gallinari P (2007) Unraveling the hidden catalytic activity of vertebrate class IIa histone deacetylases. PNAS 104(44):17335–17340Google Scholar
  15. 15.
    Kutil Z, Novakova Z, Meleshin M, Mikesova J, Schutkowski M, Barinka C (2018) Histone deacetylase 11 is a fatty-acid deacylase. ACS Chem Biol 13(3):685–693Google Scholar
  16. 16.
    Cao J, Sun L, Aramsangtienchai P, Spiegelman NA, Zhang X, Seto E, Lin H (2019) HDAC11 regulates type I interferon signaling through defatty-acylation of Shmt2. PNAS 116(12):5487–5492Google Scholar
  17. 17.
    Moreno-Yruela C, Galleano I, Madsen AS, Olsen CA (2018) Histone deacetylase 11 is an Ε-N-myristoyllysine hydrolase. Cell Chem Biol 25(7):849–856Google Scholar
  18. 18.
    Hai Y, Shinsky SA, Porter NJ, Christianson DW (2017) Histone deacetylase 10 structure and molecular function as a polyamine deacetylase. Nat Commun 8(15368):1–9Google Scholar
  19. 19.
    Riggs MG, Whittaker RG, Neumann JR, Ingram VM (1977) N-butyrate causes histone modification in HeLa and Friend erythroleukaemia cells. Nature 268(5619):462–464Google Scholar
  20. 20.
    Richon VM, Webb Y, Merger R, Sheppard T, Jursic B, Ngo L, Civoli F, Breslow R, Rifkind RA, Marks PA (1996) Second generation hybrid polar compounds are potent inducers of transformed cell differentiation. PNAS 93(12):5705–5708Google Scholar
  21. 21.
    Yoshida M, Kijima M, Akita M, Beppu T (1990) Potent and specific inhibition of mammalian histone deacetylase both in vivo and in vitro by trichostatin A. J Biol Chem 265(28):17174–17179Google Scholar
  22. 22.
    Kijima M, Yoshida M, Sugita K, Horinouchi S, Beppu T (1993) Trapoxin, an antitumor cyclic tetrapeptide, is an irreversible inhibitor of mammalian histone deacetylase. J Biol Chem 268(30):22429–22435Google Scholar
  23. 23.
    Marks PA, Breslow R (2007) Dimethyl sulfoxide to vorinostat: development of this histone deacetylase inhibitor as an anticancer drug. Nat Biotechnol 25(1):84–90Google Scholar
  24. 24.
    Zagni C, Floresta G, Monciino G, Rescifina A (2017) The search for potent, small-molecule HDAC is in cancer treatment: a decade after vorinostat. Med Res Rev 37(6):1373–1428Google Scholar
  25. 25.
    Jung M, Hoffmann K, Brosch G, Loidl P (1997) Analogues of trichosтatin A and trapoxin B as histone deacetylase inhibitors. Bioorg Med Chem Lett 7(13):1655–1658Google Scholar
  26. 26.
    Maolanon AR, Madsen AS, Olsen CA (2016) Innovative strategies for selective inhibition of histone deacetylases. Cell Chem Biol 23(7):759–768Google Scholar
  27. 27.
    Gantt SML, Decroos C, Lee MS, Gullett LE, Bowman CM, Christianson DW, Fierke CA (2016) General base–general acid catalysis in human histone deacetylase 8. Biochemistry 55(5):820–832Google Scholar
  28. 28.
    Decroos C, Christianson NH, Gullett LE, Bowman CM, Christianson KE, Deardorff MA, Christianson DW (2015) Biochemical and structural characterization of HDAC8 mutants associated with cornelia de lange syndrome spectrum disorders. Biochemistry 54(42):6501–6513Google Scholar
  29. 29.
    Dowling DP, Gantt SL, Gattis SG, Fierke CA, Christianson DW (2008) Structural studies of human histone deacetylase 8 and its site-specific variants complexed with substrate and inhibitors. Biochemistry 47(51):13554–13563Google Scholar
  30. 30.
    Lauffer BE, Mintzer R, Fong R, Mukund S, Tam C, Zilberleyb I, Flicke B, Ritscher A, Fedorowicz G, Vallero R, Ortwine DF, Gunzner J, Modrusan Z, Neumann L, Koth CM, Lupardus PJ, Kaminker JS, Heise CE, Steiner P (2013) Histone deacetylase (HDAC) inhibitor kinetic rate constants correlate with cellular histone acetylation but not transcription and cell viability. J Biol Chem 288(37):26926–26943Google Scholar
  31. 31.
    Porter NJ, Mahendran A, Breslow R, Christianson DW (2017) Unusual zinc-binding mode of HDAC6-selective hydroxamate inhibitors. PNAS 114(51):13459–13464Google Scholar
  32. 32.
    Gupta SP (2015) QSAR studies on hydroxamic acids: a fascinating family of chemicals with a wide spectrum of activities. Chem Rev 115(13):6427–6490Google Scholar
  33. 33.
    Chen K, Xu L, Wiest O (2013) Computational exploration of zinc binding groups for HDAC inhibition. J Org Chem 78(10):5051–5055Google Scholar
  34. 34.
    Wang D, Helquist P, Wiest O (2007) Zinc binding in HDAC inhibitors: a DFT study. J Org Chem 72(14):5446–5449Google Scholar
  35. 35.
    Wang D-F, Wiest O, Helquist P, Lan-Hargest H-Y, Wiech NL (2004) QSAR studies of PC-3 cell line inhibition activity of TSA and SAHA-like hydroxamic acids. Bioorg Med Chem Lett 14(3):707–711Google Scholar
  36. 36.
    Kalyaanamoorthy S, Chen Y-PP (2013) Quantum polarized ligand docking investigation to understand the significance of protonation states in histone deacetylase inhibitors. J Mol Graph Model 44:44–53Google Scholar
  37. 37.
    Wu R, Lu Z, Cao Z, Zhang Y (2011) Zinc chelation with hydroxamate in histone deacetylases modulated by water access to the linker binding channel. J Am Chem Soc 133(16):6110–6113Google Scholar
  38. 38.
    Cross JB, Duca JS, Kaminski JJ, Madison VS (2002) The active site of a zinc-dependent metalloproteinase influences the computed P K a of ligands coordinated to the catalytic zinc ion. J Am Chem Soc 124(37):11004–11007Google Scholar
  39. 39.
    Gong W, Wu R, Zhang Y (2015) Thiol versus hydroxamate as zinc binding group in HDAC inhibition: an Ab initio QM/MM molecular dynamics study. J Comput Chem 36(30):2228–2235Google Scholar
  40. 40.
    Mann BS, Johnson JR, He K, Sridhara R, Abraham S, Booth BP, Verbois L, Morse DE, Jee JM, Pope S, Harapanhalli RS, Dagher R, Farrell A, Justice R, Pazdur R (2007) Vorinostat for treatment of cutaneous manifestations of advanced primary cutaneous T-cell lymphoma. Clin Cancer Res 13(8):2318–2322Google Scholar
  41. 41.
    Day JA, Cohen SM (2013) Investigating the selectivity of metalloenzyme inhibitors. J Med Chem 56(20):7997–8007Google Scholar
  42. 42.
    Chen Y, Cohen SM (2015) Investigating the selectivity of metalloenzyme inhibitors in the presence of competing metalloproteins. ChemMedChem 10(10):1733–1738Google Scholar
  43. 43.
    Chen Y, Lai B, Zhang Z, Cohen SM (2017) The effect of metalloprotein inhibitors on cellular metal ion content and distribution. Metallomics 9(3):250–257Google Scholar
  44. 44.
    Shen S, Kozikowski AP (2016) Why hydroxamates may not be the best histone deacetylase inhibitors—what some may have forgotten or would rather forget? ChemMedChem 11(1):15–21Google Scholar
  45. 45.
    Nishino N, Jose B, Shinta R, Kato T, Komatsu Y, Yoshida M (2004) Chlamydocin–hydroxamic acid analogues as histone deacetylase inhibitors. Biorg Med Chem 12(22):5777–5784Google Scholar
  46. 46.
    Islam N, Islam S, Hoque A, Kato T, Nishino N (2015) Synthetic strategy for bicyclic tetrapeptides HDAC inhibitors using ring closing metathesis. J Chem Sci 127(9):1563–1569Google Scholar
  47. 47.
    Meinke PT, Colletti SL, Ayer MB, Darkin-Rattray SJ, Myers RW, Schmatz DM, Wyvratt MJ, Fisher MH (2000) Synthesis of side chain modified apicidin derivatives: potent mechanism-based histone deacetylase inhibitors. Tetrahedron Lett 41(41):7831–7835Google Scholar
  48. 48.
    Wen S, Carey KL, Nakao Y, Fusetani N, Packham G, Ganesan A (2007) Total synthesis of azumamide A and azumamide E, evaluation as histone deacetylase inhibitors, and design of a more potent analogue. Org Lett 9(6):1105–1108Google Scholar
  49. 49.
    Kitir B, Maolanon AR, Ohm RG, Colaço AR, Fristrup P, Madsen AS, Olsen CA (2017) Chemical editing of macrocyclic natural products provides HDAC inhibitors with picomolar affinities. Biochemistry 56(38):5134–5146Google Scholar
  50. 50.
    Thouin E, Lubell WD (2000) Effective synthesis of enantiopure hydroxamates by displacement of resin-bound esters with hydroxylamine. Tetrahedron Lett 41(4):457–460Google Scholar
  51. 51.
    Floyd CD, Lewis CN, Patel SR, Whittaker M (1996) A method for the synthesis of hydroxamic acids on solid phase. Tetrahedron Lett 37(44):8045–8048Google Scholar
  52. 52.
    Ngu K, Patel DV (1997) A new and efficient solid phase synthesis of hydroxamic acids. J Org Chem 62(21):7088–7089Google Scholar
  53. 53.
    Gordeev MF, Hui HC, Gordon EM, Patel DV (1997) A general and efficient solid phase synthesis of quinazoline-2, 4-diones. Tetrahedron Lett 38(10):1729–1732Google Scholar
  54. 54.
    Chen JJ, Spatola AF (1997) Solid phase synthesis of peptide hydroxamic acids. Tetrahedron Lett 38(9):1511–1514Google Scholar
  55. 55.
    Richter LS, Desai MC (1997) A TFA-cleavable linkage for solid-phase synthesis of hydroxamic acids. Tetrahedron Lett 38(3):321–322Google Scholar
  56. 56.
    Barlaam B, Koza P, Berriot J (1999) Solid-phase synthesis of hydroxamic acid based TNF-α convertase inhibitors. Tetrahedron 55(23):7221–7232Google Scholar
  57. 57.
    Mellor SL, McGuire C, Chan WC (1997) N-Fmoc-aminooxy-2-chlorotrityl polystyrene resin: a facile solid-phase methodology for the synthesis of hydroxamic acids. Tetrahedron Lett 38(18):3311–3314Google Scholar
  58. 58.
    Bauer U, Ho W-B, Koskinen AM (1997) A novel linkage for the solid-phase synthesis of hydroxamic acids. Tetrahedron Lett 38(41):7233–7236Google Scholar
  59. 59.
    Bang CG, Jensen JF, O’Hanlon Cohrt E, Olsen LB, Siyum SG, Mortensen KT, Skovgaard T, Berthelsen J, Yang L, Givskov M (2017) A linker for the solid-phase synthesis of hydroxamic acids and identification of HDAC6 inhibitors. ACS Comb Sci 19(10):657–669Google Scholar
  60. 60.
    Montero A, Beierle JM, Olsen CA, Ghadiri MR (2009) Design, synthesis, biological evaluation, and structural characterization of potent histone deacetylase inhibitors based on cyclic Α/Β-tetrapeptide architectures. J Am Chem Soc 131(8):3033–3041Google Scholar
  61. 61.
    Olsen CA, Ghadiri MR (2009) Discovery of potent and selective histone deacetylase inhibitors via focused combinatorial libraries of cyclic Α3β-tetrapeptides. J Med Chem 52(23):7836–7846Google Scholar
  62. 62.
    Watson PJ, Millard CJ, Riley AM, Robertson NS, Wright LC, Godage HY, Cowley SM, Jamieson AG, Potter BVL, Schwabe JWR (2016) Insights into the activation mechanism of class I HDAC complexes by inositol phosphates. Nat Commun 7(11262):1–13Google Scholar
  63. 63.
    Wilson DM, Silverman LN, Bergauer M, Keshari KR (2013) Solid phase synthesis of hydroxamate peptides for histone deacetylase inhibition. Tetrahedron Lett 54(2):151–153Google Scholar
  64. 64.
    Dose A, Sindlinger J, Bierlmeier J, Bakirbas A, Schulze-Osthoff K, Einsele-Scholz S, Hartl M, Essmann F, Finkemeier I, Schwarzer D (2016) Interrogating substrate selectivity and composition of endogenous histone deacetylase complexes with chemical probes. Angew Chem Int Ed 55(3):1192–1195Google Scholar
  65. 65.
    Nielsen DS, Shepherd NE, Xu W, Lucke AJ, Stoermer MJ, Fairlie DP (2017) Orally absorbed cyclic peptides. Chem Rev 117(12):8094–8128Google Scholar
  66. 66.
    Craik DJ, Fairlie DP, Liras S, Price D (2013) The future of peptide-based drugs. Chem Biol Drug Des 81(1):136–147Google Scholar
  67. 67.
    Maolanon A, Kristensen H, Leman L, Ghadiri R, Olsen CA (2017) Natural and synthetic macrocyclic inhibitors of the histone deacetylase enzymes. ChemBioChem 18(1):5–49Google Scholar
  68. 68.
    Furumai R, Komatsu Y, Nishino N, Khochbin S, Yoshida M, Horinouchi S (2001) Potent histone deacetylase inhibitors built from trichostatin A and cyclic tetrapeptide antibiotics including trapoxin. PNAS 98(1):87–92Google Scholar
  69. 69.
    Yoshida M, Furumai R, Nishiyama M, Komatsu Y, Nishino N, Horinouchi S (2001) Histone deacetylase as a new target for cancer chemotherapy. Cancer Chemother Pharmacol 48:S20–S26Google Scholar
  70. 70.
    Komatsu Y, Tomizaki K-Y, Tsukamoto M, Kato T, Nishino N, Sato S, Yamori T, Tsuruo T, Furumai R, Yoshida M, Horinouchi S, Hayashi H (2001) Cyclic hydroxamic-acid-containing peptide 31, a potent synthetic histone deacetylase inhibitor with antitumor activity. Cancer Res 61(11):4459–4466Google Scholar
  71. 71.
    Wang S, Li X, Wei Y, Xiu Z, Nishino N (2014) Discovery of potent HDAC inhibitors based on chlamydocin with inhibitory effects on cell migration. ChemMedChem 9(3):627–637Google Scholar
  72. 72.
    Islam NM, Kato T, Nishino N, Kim H-J, Ito A, Yoshida M (2010) Bicyclic peptides as potent inhibitors of histone deacetylases: optimization of alkyl loop length. Bioorg Med Chem Lett 20(3):997–999Google Scholar
  73. 73.
    Li X-H, Huang M-L, Wang S-M, Wang Q (2013) Selective inhibition of bicyclic tetrapeptide histone deacetylase inhibitor on HDAC4 and K562 leukemia cell. Asian Pac J Cancer Prev 14(12):7095–7100Google Scholar
  74. 74.
    Jose B, Okamura S, Kato T, Nishino N, Sumida Y, Yoshida M (2004) Toward an HDAC6 inhibitor: synthesis and conformational analysis of cyclic hexapeptide hydroxamic acid designed from α-tubulin sequence. Biorg Med Chem 12(6):1351–1356Google Scholar
  75. 75.
    Nakao Y, Yoshida S, Matsunaga S, Shindoh N, Terada Y, Nagai K, Yamashita JK, Ganesan A, van Soest RWM, Fusetani N (2006) Azumamides A–E: histone deacetylase inhibitory cyclic tetrapeptides from the marine sponge mycale izuensis. Angew Chem Int Ed 45(45):7553–7557Google Scholar
  76. 76.
    Maulucci N, Chini MG, Di Micco S, Izzo I, Cafaro E, Russo A, Gallinari P, Paolini C, Nardi MC, Casapullo A (2007) Molecular insights into azumamide E histone deacetylases inhibitory activity. J Am Chem Soc 129(10):3007–3012Google Scholar
  77. 77.
    Kranz M, Murray PJ, Taylor S, Upton RJ, Clegg W, Elsegood MRJ (2006) Solution, solid phase and computational structures of apicidin and its backbone-reduced analogs. J Pept Sci 12(6):383–388Google Scholar
  78. 78.
    Izzo I, Maulucci N, Bifulco G, De Riccardis F (2006) Total synthesis of azumamides A and E. Angew Chem Int Ed 45(45):7557–7560Google Scholar
  79. 79.
    Kawai M, Jasensky RD, Rich DH (1983) Conformational analysis by NMR spectrometry of the highly substituted cyclic tetrapeptides, chlamydocin and Ala4-chlamydocin. Evidence for a unique amide bond sequence in dimethyl sulfoxide-d6. J Am Chem Soc 105(13):4456–4462Google Scholar
  80. 80.
    Rich DH, Kawai M, Jasensky RD (1983) Conformational studies of cyclic tetrapeptides. Chem Biol Drug Des 21(1):35–42Google Scholar
  81. 81.
    Kawai M, Rich DH, Walton JD (1983) The structure and conformation of HC-toxin. Biochem Biophys Res Commun 111(2):398–403Google Scholar
  82. 82.
    Taura K, Yamamoto Y, Nakajima A, Hata K, Uchinami H, Yonezawa K, Hatano E, Nishino N, Yamaoka Y (2004) Impact of novel histone deacetylase inhibitors, CHAP31 and FR901228 (FK228), on adenovirus-mediated transgene expression. J Gene Med 6(5):526–536Google Scholar
  83. 83.
    Yasukawa K, Sawamura D, Goto M, Nakamura H, Shimizu H (2007) Histone deacetylase inhibitors preferentially augment transient transgene expression in human dermal fibroblasts. Br J Dermatol 157(4):662–669Google Scholar
  84. 84.
    Murakami K, Matsubara H, Hoshino I, Akutsu Y, Miyazawa Y, Matsushita K, Sakata H, Nishimori T, Usui A, Kano M, Nishino N, Yoshida M (2010) CHAP31 induces apoptosis only via the intrinsic pathway in human esophageal cancer cells. Oncology 78(1):62–74Google Scholar
  85. 85.
    Isozaki Y, Hoshino I, Nohata N, Kinoshita T, Akutsu Y, Hanari N, Mori M, Yoneyama Y, Akanuma N, Takeshita N, Maruyama T, Seki N, Nishino N, Yoshida M, Matsubara H (2012) Identification of novel molecular targets regulated by tumor suppressive miR-375 induced by histone acetylation in esophageal squamous cell carcinoma. Int J Oncol 41(3):985–994Google Scholar
  86. 86.
    Fujii S, Okinaga T, Ariyoshi W, Takahashi O, Iwanaga K, Nishino N, Tominaga K, Nishihara T (2013) Mechanisms of G1 cell cycle arrest and apoptosis in myeloma cells induced by hybrid-compound histone deacetylase inhibitor. Biochem Biophys Res Commun 434(3):413–420Google Scholar
  87. 87.
    Hutt DM, Olsen CA, Vickers CJ, Herman D, Chalfant MA, Montero A, Leman LJ, Burkle R, Maryanoff BE, Balch WE, Ghadiri MR (2011) Potential agents for treating cystic fibrosis: cyclic tetrapeptides that restore trafficking and activity of ΔF508-CFTR. ACS Med Chem Lett 2(9):703–707Google Scholar
  88. 88.
    Lai J-I, Leman LJ, Ku S, Vickers CJ, Olsen CA, Montero A, Ghadiri MR, Gottesfeld JM (2017) Cyclic tetrapeptide HDAC inhibitors as potential therapeutics for spinal muscular atrophy: screening with IPSC-derived neuronal cells. Bioorg Med Chem Lett 27(15):3289–3293Google Scholar
  89. 89.
    Kahnberg P, Lucke AJ, Glenn MP, Boyle GM, Tyndall JD, Parsons PG, Fairlie DP (2006) Design, synthesis, potency, and cytoselectivity of anticancer agents derived by parallel synthesis from α-aminosuberic acid. J Med Chem 49(26):7611–7622Google Scholar
  90. 90.
    Andrews KT, Tran TN, Lucke AJ, Kahnberg P, Le GT, Boyle GM, Gardiner DL, Skinner-Adams TS, Fairlie DP (2008) Potent antimalarial activity of histone deacetylase inhibitor analogues. Antimicrob Agents Chemother 52(4):1454–1461Google Scholar
  91. 91.
    Taddei M, Cini E, Giannotti L, Giannini G, Battistuzzi G, Vignola D, Vesci L, Cabri W (2014) Lactam based 7-amino suberoylamide hydroxamic acids as potent HDAC inhibitors. Bioorg Med Chem Lett 24(1):61–64Google Scholar
  92. 92.
    Krieger V, Hamacher A, Gertzen CG, Senger J, Zwinderman MR, Marek M, Romier C, Dekker FJ, Kurz T, Jung M, Gohlke H, Kassack MU, Hansen FK (2017) Design, multicomponent synthesis and anticancer activity of a focused histone deacetylase (HDAC) inhibitor library with peptoid-based cap groups. J Med Chem 60(13):5493–5506Google Scholar
  93. 93.
    Belvedere S, Witter DJ, Yan J, Secrist JP, Richon V, Miller TA (2007) Aminosuberoyl hydroxamic acids (ASHAs): a potent new class of HDAC inhibitors. Bioorg Med Chem Lett 17(14):3969–3971Google Scholar
  94. 94.
    Watson PJ, Fairall L, Santos GM, Schwabe JW (2012) Structure of HDAC3 bound to corepressor and inositol tetraphosphate. Nature 481(7381):335–340Google Scholar
  95. 95.
    Millard CJ, Watson PJ, Celardo I, Gordiyenko Y, Cowley SM, Robinson CV, Fairall L, Schwabe JWR (2013) Class I HDACs share a common mechanism of regulation by inositol phosphates. Mol Cell 51(1):57–67Google Scholar
  96. 96.
    Bantscheff M, Hopf C, Savitski MM, Dittmann A, Grandi P, Michon A-M, Schlegl J, Abraham Y, Becher I, Bergamini G, Boesche M, Delling M, Dümpelfeld B, Eberhard D, Huthmacher C, Mathieson T, Poeckel D, Reader V, Strunk K, Sweetman G, Kruse U, Neubauer G, Ramsden NG, Drewes G (2011) Chemoproteomics profiling of HDAC inhibitors reveals selective targeting of HDAC complexes. Nat Biotechnol 29(3):255–265Google Scholar
  97. 97.
    Becher I, Dittmann A, Savitski MM, Hopf C, Drewes G, Bantscheff M (2014) Chemoproteomics reveals time-dependent binding of histone deacetylase inhibitors to endogenous repressor complexes. ACS Chem Biol 9(8):1736–1746Google Scholar
  98. 98.
    Sindlinger J, Bierlmeier J, Geiger LC, Kramer K, Finkemeier I, Schwarzer D (2016) Probing the structure–activity relationship of endogenous histone deacetylase complexes with immobilized peptide-inhibitors. J Pept Sci 22(5):352–359Google Scholar
  99. 99.
    Wu M, Hayward D, Kalin JH, Song Y, Schwabe JWR, Cole PA (2018) Lysine-14 acetylation of histone H3 in chromatin confers resistance to the deacetylase and demethylase activities of an epigenetic silencing complex. eLife 7:e37231Google Scholar

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© Springer Nature Switzerland AG  2019

Authors and Affiliations

  1. 1.Department of Drug Design and Pharmacology, Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagenDenmark

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