Development of a high-throughput screening-compatible assay for the discovery of inhibitors of the af4-af9 interaction using alphascreen technology

Assay and Drug Development Technologies

Volumn 11, Issue 4, 2013, Pages 253-268

  Watson, Venita Gresham ^a,b   Drake, Katherine M ^a   Peng, Yu ^a   Napper, Andrew D ^a  

^a NEMOURS ALFRED I DUPONT HOSPITAL FOR CHILDREN   (United States)

^b Department of Structural Biology   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CELL PENETRATING PEPTIDE; HYBRID PROTEIN; MIXED LINEAGE LEUKEMIA PROTEIN; MLL AF4 PROTEIN; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR AF4; TRANSCRIPTION FACTOR AF9; UNCLASSIFIED DRUG;

ARTICLE; ARTIFACT; BIOTINYLATION; CELL DEATH; CHROMOSOME REARRANGEMENT; DRUG DETERMINATION; HIGH THROUGHPUT SCREENING; HUMAN; LEUKEMIA; LEUKEMIA CELL; PILOT STUDY; PROTEIN BINDING; PROTEIN PROTEIN INTERACTION; SENSITIVITY ANALYSIS; SIGNAL NOISE RATIO; VALIDATION PROCESS;

DNA-BINDING PROTEINS; DRUG DISCOVERY; HIGH-THROUGHPUT SCREENING ASSAYS; MYELOID-LYMPHOID LEUKEMIA PROTEIN; NUCLEAR PROTEINS; ONCOGENE PROTEINS, FUSION; PROTEIN BINDING; PROTEIN INTERACTION MAPPING;

EID: 84880196662     PISSN: 1540658X     EISSN: 15578127     Source Type: Journal    
DOI: 10.1089/adt.2012.495     Document Type: Article

References (29)

1. Mackall CL: In search of targeted therapies for childhood cancer. Front Oncol 2011;1:18.
2. Slany RK: The molecular biology of mixed lineage leukemia. Haematologica 2009;94:984-993.
3. Robinson BW, Devidas M, Carroll AJ, et al.: Specific MLL partner genes in infant acute lymphoblastic leukemia (ALL) associated with outcome are linked to age and white blood cell count (WBC) at diagnosis: a report on the Children's Oncology Group (COG) P9407 Trial. American Society of Hematology Annual Meeting and Exposition. New Orleans, LA, 2009.
4. Meyer C, Kowarz E, Hofmann J, et al.: New insights to the MLL recombinome of acute leukemias. Leukemia 2009;23:1490-1499.
5. Armstrong SA, Staunton JE, Silverman LB, et al.: MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia. Nat Genet 2002;30:41-47.
6. Armstrong SA, Golub TR, Korsmeyer SJ: MLL-rearranged leukemias: insights from gene expression profiling. Semin Hematol 2003,40:268-273.
7. Faber J, Krivtsov AV, Stubbs MC, et al.: HOXA9 is required for survival in human MLL-rearranged acute leukemias. Blood 2009;113:2375-2385.
8. Bitoun E, Oliver PL, Davies KE: The mixed-lineage leukemia fusion partner AF4 stimulates RNA polymerase II transcriptional elongation and mediates coordinated chromatin remodeling. Hum Mol Genet 2007;16:92-106.
9. Monroe SC, Jo SY, Sanders DS, et al.: MLL-AF9 and MLL-ENL alter the dynamic association of transcriptional regulators with genes critical for leukemia. Exp Hematol 2011;39:77-86, e71-75.
10. Huret JL, Dessen P, Bernheim A: An atlas of chromosomes in hematological malignancies. Example: 11q23 and MLL partners. Leukemia 2001;15:987-989.
11. Meyer C, Schneider B, Jakob S, et al.: The MLL recombinome of acute leukemias. Leukemia 2006;20:777-784.
12. Erfurth F, Hemenway CS, de Erkenez AC, Domer PH: MLL fusion partners AF4 and AF9 interact at subnuclear foci. Leukemia 2004;18:92-102.
13. Srinivasan RS, Nesbit JB, Marrero L, Erfurth F, LaRussa VF, Hemenway CS: The synthetic peptide PFWT disrupts AF4-AF9 protein complexes and induces apoptosis in t(4;11) leukemia cells. Leukemia 2004;18:1364-1372.
14. Palermo CM, Bennett CA, Winters AC, Hemenway CS: The AF4-mimetic peptide, PFWT, induces necrotic cell death in MV4-11 leukemia cells. Leuk Res 2008;32:633-642.
15. Bennett CA, Winters AC, Barretto NN, Hemenway CS: Molecular targeting of MLL-rearranged leukemia cell lines with the synthetic peptide PFWT synergistically enhances the cytotoxic effect of established chemotherapeutic agents. Leuk Res 2009;33:937-947.
16. Kazmierski WM, Kenakin TP, Gudmundsson KS: Peptide, peptidomimetic and small-molecule drug discovery targeting HIV-1 host-cell attachment and entry through gp120, gp41, CCR5 and CXCR4{. Chem Biol Drug Des 2006; 67:13-26.
17. MicroSource Spectrum Collection. www.msdiscovery.com/spectrum.html (last accessed on October 22, 2012).
18. TimTec Nature Inspired Screening Libraries. www.TimTec.net/Natural- Products .html (last accessed on October 22, 2012).
19. Zhang JH, Chung TD, Oldenburg KR: A simple statistical parameter for use in evaluation and validation of high throughput screening assays. J Biomol Screen 1999;4:67-73.
20. Perkin Elmer: A Practical Guide to Working with Alpha Screen. PerkinElmer LAS literature 00701101. Boston: Perkin Elmer, 2004.
21. Arkin MR, Glicksman MA, Fu H, Havel JJ, Du Y: Inhibition of protein-protein interactions: non-cellular assay formats. In: Assay Guidance Manual. Sittampalam GS, Gal-Edd N, Arkin MR, (eds.). Eli Lilly & Company and the National Center for Advancing Translational Sciences, Bethesda, MD, 2012. www.ncbi.nlm.nih.gov/books/NBK92000 (last accessed on November 2, 2012).
22. PerkinElmer: User's Guide to Alpha Assays Protein:Protein Interactions. PerkinElmer LAS literature 00962501. Boston: PerkinElmer, 2011.
23. Leach BI, Kuntimaddi A, Schmidt CR, Cierpicki T, Johnson SA, Bushweller JH: Leukemia fusion target AF9 is an intrinsically disordered transcriptional regulator that recruits multiple partners via coupled folding and binding. Structure 8;21:176-183.
24. Eastwood BJ, Farmen MW, Iversen PW, et al.: The minimum significant ratio: a statistical parameter to characterize the reproducibility of potency estimates from concentration-response assays and estimation by replicate-experiment studies. J Biomol Screen 2006;11:253-261.
25. Schurer SC, Vempati U, Smith R, Southern M, Lemmon V: BioAssay ontology annotations facilitate cross-analysis of diverse high-throughput screening data sets. J Biomol Screen 2011;16:415-426.
26. Baell JB, Holloway GA: New substructure filters for removal of pan assay interference compounds (PAINS) from screening libraries and for their exclusion in bioassays. J Med Chem 2010;53:2719-2740.
27. Mayasundari A, Ferreira AM, He L, Mahindroo N, Bashford D, Fujii N: Rational design of the first small-molecule antagonists of NHERF1/EBP50 PDZ domains. Bioorg Med Chem Lett 2008;18:942-945.
28. Niesen FH, Berglund H, Vedadi M: The use of differential scanning fluorimetry to detect ligand interactions that promote protein stability. Nat Protoc 2007;2:2212-2221.
29. Lee EM, Bachmann PS, Lock RB: Xenograft models for the preclinical evaluation of new therapies in acute leukemia. Leuk Lymphoma 2007;48:659-668.