2017-2011

Our publications from 2017 up to 2011

69. Hughes, S.J., Ciulli, A.*

Molecular recognition of ternary complexes: a new dimension in the structure-guided design of chemical degraders

Essays Biochem. 2017, 61, 505-516

 

68. Maniaci, C., Hughes, S.J., Testa, A., Chen, W., Lamont, D.J., Rocha, S., Alessi, D.R., Romeo, R., Ciulli, A.*

Homo-PROTACs: bivalent small-molecule dimerizers of the VHL E3 ubiquitin ligase to induce self-degradation

Nat. Commun. 2017, 8, 830

  • See Figures here
  • Our VHL dimerizer/degrader CM11 and inactive epimer CMP98 are available from Tocris (April 2018)
  • Find out more about CM11 in the Chemical Probes Portal
  • Highlighted as “Promising PROTAC” in the 2020s Top Probes list of the Chemical Probes Portal

 

67. Morreale, F.E., Testa, A., Chaugule, V.K., Bortoluzzi, A., Ciulli, A.*, Walden, H.*

Mind the metal: a fragment library-derived zinc impurity binds the E2 ubiquitin-conjugating enzyme Ube2T and induces structural rearrangements

J. Med. Chem. 2017, 60 (19), 8183-8191

 

66. Soares, P., Gadd, M.S., Frost, J., Galdeano, C., Ellis, L.C.J., Epemolu, O., Rocha, S., Read, K.D., Ciulli, A.*

Group-based optimization of potent and cell-active inhibitors of the von Hippel-Lindau (VHL) E3 ubiquitin ligase: structure-activity relationships leading to the chemical probe (2S,4R)-1-((S)-2-(1-cyanocyclopropanecarboxamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (VH298)

J. Med. Chem. 2018, 61 (2), 599-618

 

65. Khan, R., Marsh, G., Felix, R., Kemmitt, P.D., Baud, M.G.J., Ciulli, A., Spencer, J.

Gram-Scale Laboratory Synthesis of TC AC 28, a High-Affinity BET Bromodomain Ligand

ACS Omega 2017, 2 (8), 4328–4332

 

64. Cardote, T.A.F., Ciulli, A.*

Structure-guided design of peptides as tools to probe the protein-protein interaction between Cullin-2 and Elongin BC substrate adaptor in Cullin RING E3 ubiquitin ligases

ChemMedChem 2017, 12 (18), 1491-1496

 

63. Chan, K.-H., Zengerle, M., Testa, A., Ciulli, A.*

Impact of Target Warhead and Linkage Vector on Inducing Protein Degradation: Comparison of Bromodomain and Extra-Terminal (BET) Degraders Derived from Triazolodiazepine (JQ1) and Tetrahydroquinoline (I-BET726) BET Inhibitor Scaffolds

J. Med. Chem. 2018, 61 (2), 504-513

 

62. Cardote, T.A.F., Gadd, M.S., Ciulli, A.*

Crystal Structure of the Cul2-Rbx1-EloBC-VHL Ubiquitin Ligase Complex

Structure 2017, 25 (6), 901-911.e3

  • See Figures here
  • Featured in the SLS News website
  • Access the coordinates of our pentameric complex crystal structure in the Protein DataBank: PDB entry code is 5N4W

 

61. Fernandez-Alonso, R., Davidson, L., Hukelmann, J., Zengerle, M., Prescott, A.R., Lamond, A., Ciulli, A., Sapkota, G.P., Findlay, G.M.

Brd4-Brd2 isoform switching coordinates pluripotent exit and Smad2-dependent lineage specification

EMBO Reports 2017, 18 (7), 1108-1122

 

60. Morreale, F.E., Bortoluzzi, A., Chaugule, V.K., Arkinson, C., Walden, H.*, Ciulli, A.*

Allosteric targeting of the Fanconi anemia ubiquitin-conjugating enzyme Ube2T by fragment screening

J. Med. Chem. 2017, 60 (9), 4093-4098

 

59. Ryan, A., Polycarpou, E., Lack, N.A., Evangelopoulos, D., Sieg, C., Halman, A., Bhakta, S., Eleftheriadou, O., McHugh, T.D., Keany, S., Lowe, E.D., Ballet, R., Abuhammad, A., Jacobs, W.R. Jr, Ciulli, A., Sim, E.

Investigation of the mycobacterial enzyme HsaD as a potential novel target for anti-tubercular agents using a fragment-based drug design approach

Br. J. Pharmacol. 2017, 174 (14), 2209-2224

 

58. Bortoluzzi, A., Amato, A., Lucas, X., Blank, M., Ciulli, A.*

Structural Basis of Molecular Recognition of Helical Histone H3 Tail by PHD Finger Domains

Biochem. J. 2017, 474 (10), 1633-1651

  • See Figures here
  • Access the coordinates of our domain-peptide complex crystal structure in the Protein Data Bank: PDB entry code is 5T8R

 

57. Gadd, M.S., Testa, A., Lucas, X., Chan, K.-H., Chen, W., Lamont, D.J., Zengerle, M., Ciulli, A.*

Structural basis of PROTAC cooperative recognition for selective protein degradation

Nat. Chem. Biol. 2017, 13 (5), 514-521

 

56. De Schutter, J.W., Morrison, J.P., Morrison, M.J., Ciulli, A., Imperiali, B.

Targeting Bacillosamine Biosynthesis in Bacterial Pathogens: Development of Inhibitors to a Bacterial Amino-Sugar Acetyltransferase from Campylobacter jejuni

J. Med. Chem. 2017, 60 (5), 2099-2118

 

55. Lucas, X., Ciulli, A.*

Recognition of substrate degrons by E3 ubiquitin ligases and modulation by small-molecule mimicry strategies

Curr. Opin. Struct. Biol. 2017, 44, 101-110

 

54. Frost, J., Galdeano, C., Soares, P., Gadd, M.S., Epemolu, O., Grzes, K., Ellis, L., Shimamura, S., Bantscheff, M., Grandi, P., Read, K.D., Cantrell, D.A., Rocha, S., Ciulli, A.*

Potent and selective chemical probe of hypoxic signalling downstream of HIF-α hydroxylation via VHL inhibition

Nat. Commun. 2016, 7, 13312

  • See Figures here
  • Featured in the UoD and SLS News websites
  • Highlighted in Drug Discovery Today and Phys.org
  • Access the coordinates of our protein-ligand co-crystal structure in the Protein DataBank: PDB entry code is 5LLI
  • FInd out more about VH298 in the Chemical Probes Portal
  • Our VHL inhibitor VH298 and inactive epimer cis-VH298 are available from Tocris (from April 2017)

 

53. Ciulli, A.*

Target validation: Switching domains

Nat. Chem. Biol. 2016, 12 (9), 659-660

 

52. Runcie, A.C., Chan, K.-H., Zengerle, M., Ciulli, A.*

Chemical genetics approaches for selective intervention in epigenetics

Curr. Opin. Chem. Biol. 2016, 33, 186-194

 

51. Galdeano, C., Ciulli, A.*

Selectivity on-target of bromodomain chemical probes by structure-guided medicinal chemistry and chemical biology

Future Med. Chem. 2016, 8 (13), 1655-1680

47. Gadd, M.S., Bulatov, E., Ciulli, A.*

Serendipitous SAD Solution for DMSO-Soaked SOCS2-ElonginC-ElonginB Crystals Using Covalently Incorporated Dimethylarsenic: Insights into Substrate Receptor Conformational Flexibility in Cullin RING Ligases

PLoS ONE June 29, 2015; 10(6):e013218

 

46. Zengerle, M., Chan, K.-H., Ciulli, A.*

Selective small molecules induced degradation of the BET bromodomain protein BRD4

ACS Chem. Biol. 2015, 10 (8), 1770-1777

  • See Figures here
  • Featured in the UoD and CLS News websites
  • Featured in BBC News
  • Listed amongst Most Read Articles in ACS Chem. Biol. (1 and 12 months frameworks)
  • Find out more about MZ1 in the Chemical Probes Portal
  • Our Brd4 degrader PROTAC MZ1 and the inactive epimer cis-MZ1 are available from Tocris (from April 2017)
  • MZ1 (and cis-MZ1) are available from Boehringer Ingelheim’s OpnMe Portal: order for free, no strings attached!

 

45. Bulatov, E., Ciulli, A.*

Targeting Cullin-RING E3 ubiquitin ligases for drug discovery: Structure, assembly and small molecule modulation

Biochem. J. 2015, 467 (3), 365-386

 

44. Tallant, C., Valentini, E. Fedorov, O., Overvoorde, L., Ferguson, F.M., Filippakopoulos, P., Svergun, D.I., Knapp, S., Ciulli, A.*

Molecular basis of histone tail recognition by human TIP5 PHD finger and Bromodomain of the chromatin remodelling complex NoRC

Structure 2015, 23 (1), 80-92

 

43. Bulatov, E., Martin, E.M., Chatterjee, S., Knebel, A., Shimamura, S., Konijnenberg, A., Johnson, C., Zinn, N., Grandi, P., Sobott, F., Ciulli, A.*

Biophysical studies on interactions and assembly of full-size E3 ubiquitin ligase: suppressor of cytokine signaling 2 (SOCS2):ElonginBC:Cullin5:RING-box protein 2 (Rbx2)

J. Biol. Chem. 2015, 290 (7), 4178-4191

 

42. Baud, M.G., Lin-Shiao, E., Cardote, T., Tallant, C., Pschibul, A., Chan, K.H., Zengerle, M., Garcia, J.R., Kwan, T.T., Ferguson, F.M., Ciulli, A.*

A bump-and-hole approach to engineer controlled selectivity of BET bromodomain chemical probes

Science 2014, 346 (6209), 638-641

 

41. Ferguson, F.M., Dias, D.M., Rodrigues, J.P., Wienk, H., Boelens, R., Bonvin, A.M., Abell C., Ciulli A.*

Binding Hotspots of BAZ2B Bromodomain: Histone Interaction Revealed by Solution NMR Driven Docking

Biochemistry 2014, 53 (42), 6706-6716

  •  See Figures here

 

40. Galdeano, C., Gadd, M.S., Soares, P., Scaffidi, S., Van Molle, I., Birced, I., Hewitt, S., Dias, D.M., Ciulli A.*

Structure-Guided Design and Optimization of Small Molecules Targeting the Protein-Protein Interaction between the von Hippel-Lindau (VHL) E3 Ubiquitin Ligase and the Hypoxia Inducible Factor (HIF) Alpha Subunit with In Vitro Nanomolar Affinities

J. Med. Chem. 2014, 57 (20), 8657-8663

  • See Figures here
  • Top Most Read Article in the journal (12 months timeframe)
  • Our VHL ligand VH032-amide and its inactive epimer cis-VH032, as well as various functionalized versions e.g. VHL-ligand plus linkers are available from Tocris
  • Access the coordinates of our VHL-liganded co-crystal structures in the Protein DataBank: PDB entry codes are 4W9C, 4W9D, 4W9E, 4W9F, 4W9G, 4W9H (VHL bound to ligand 7, aka VH032), 4W9I, 4W9J, 4W9K and 4W9L

 

39. Dias, D.M., Ciulli, A.*

NMR approaches in structure-based lead discovery: Recent developments and new frontiers for targeting multi-protein complexes

Prog. Biophys. Mol. Biol. 2014, 116 (2-3), 101-112

 

38. Dias, D.M., Van Molle, I., Baud, M.G.J., Galdeano, C., Geraldes, C.F.G.C., Ciulli, A.*

Is NMR Fragment Screening Fine-Tuned to Assess Druggability of Protein-Protein Interactions?

ACS Med. Chem. Lett. 2014, 5 (1), 23-28

  • See Figures here
  • Highlighted in Practical Fragments
  • 4th Most-Read Article in ACS Med. Chem. Lett. (Nov-Dec 2013)

 

37. Ferguson, F.M., Fedorov, O., Chaikuad, A., Philpott, M., Muniz, J., Felletar, I., von Delft, F., Heightman, T.D., Knapp, S., Abell, C., Ciulli, A.*

Targeting Low-Druggability Bromodomains: Fragment Based Screening and Inhibitor Design Against the BAZ2B Bromodomain

J. Med. Chem. 2013, 56 (24), 10183-10187

 

36. Thomas, J.C., Matak-Vinkovic, D., Van Molle, I., Ciulli, A.*

Multimeric Complexes among Ankyrin-Repeat and SOCS-box Protein 9 (ASB9), ElonginBC, and Cullin 5: Insights into the Structure and Assembly of ECS-type Cullin-RING E3 Ubiquitin Ligases

Biochemistry 2013, 52 (31), 5236-5246

 

35. Van Molle, I., Thomann, A., Buckley, D.L., So, E.C., Lang, S., Crews, C.M., Ciulli, A.*

Dissecting Fragment-Based Lead Discovery at the von-Hippel Lindau Protein : Hypoxia Inducible Factor 1α Protein-Protein Interface

Chem. Biol. 2012, 19, 1300-1312

 

34. Buckley, D.L., Gustafson, J.L., Van Molle, I., Roth, A.G., Tae, H.S., Gareiss, P.C., Jorgensen, W.L., Ciulli, A., Crews, C.M.

Small Molecules Inhibitors of the Interaction Between the E3 Ligase VHL and HIF1α

Angew. Chem. Int. Ed. 2012, 51, 11463-11467

  • Selected as a “Hot paper” by the Editors of Angew. Chem. and Angew. Chem. Int. Ed.

 

33. Buckley, D.L., Van Molle, I., Gareiss, P.C., Tae, H.S., Michel, J., Noblin, D.J., Jorgensen, W.L., Ciulli, A.,* Crews, C.M.*

Targeting the von Hippel-Lindau E3 Ubiquitin Ligase Using Small Molecules to Disrupt the VHL/HIF-1α Interaction

J. Am. Chem. Soc. 2012, 134, 4465–4468

 

32. Philpott, M., Yang, J., Tumber, T., Fedorov, O., Uttarkar, S., Filippakopoulos, P., Picaud, S., Keates, T., Felletar, I., Ciulli, A., Knapp, S., Heightman, T.D.

Bromodomain-peptide displacement assays for interactome mapping and inhibitor discovery

Mol. Biosyst. 2011, 7, 2899–2908

  • Top Most-Accessed Article in August 2011