A protein-targeting strategy used to develop a selective inhibitor of the E17K point mutation in the PH domain of Akt1

Nature Chemistry

Volumn 7, Issue 5, 2015, Pages 455-462

  Deyle, Kaycie M ^a   Farrow, Blake ^b   Qiao Hee, Ying ^a   Work, Jeremy ^a   Wong, Michelle ^a   Lai, Bert ^c   Umeda, Aiko ^a   Millward, Steven W ^d   Nag, Arundhati ^a   Das, Samir ^a   Heath, James R ^a  

^a CALIFORNIA INSTITUTE OF TECHNOLOGY   (United States)

^b California Institute of Technology   (United States)

^c Indi Molecular   (United States)

^d UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AKT1 PROTEIN, HUMAN; EPITOPE; LIGAND; PROTEIN BINDING; PROTEIN KINASE B;

AMINO ACID SEQUENCE; CHEMISTRY; GENETICS; METABOLISM; MOLECULAR GENETICS; POINT MUTATION;

AMINO ACID SEQUENCE; EPITOPES; LIGANDS; MOLECULAR SEQUENCE DATA; POINT MUTATION; PROTEIN BINDING; PROTO-ONCOGENE PROTEINS C-AKT;

EID: 84928530619     PISSN: 17554330     EISSN: 17554349     Source Type: Journal    
DOI: 10.1038/nchem.2223     Document Type: Article

References (27)

1. Rusling, J. F., Kumar, C. V., Gutkind, J. S. & Patel, V. Measurement of biomarker proteins for point-of-care early detection and monitoring of cancer. Analyst 135, 2496-2511 (2010).
2. Chong, C. R. & Janne, P. A. The quest to overcome resistance to EGFR-targeted therapies in cancer. Nature Med. 19, 1389-1400 (2013).
3. Tjin Tham Sjin, R. et al. In vitro and in vivo characterization of irreversible mutant-selective EGFR inhibitors that are wild-type sparing. Mol. Cancer Ther. 13, 1468-1479 (2014).
4. Capper, D., Zentgraf, H., Balss, J., Hartmann, C. & von Deimling, A. Monoclonal antibody specific for IDH1 R132H mutation. Acta Neuropathol. 118, 599-601 (2009).
5. Yu, J. et al. Mutation-specific antibodies for the detection of EGFR mutations in non-small-cell lung cancer. Clin. Cancer Res. 15, 3023-3028 (2009).
6. Capper, D. et al. Assessment of BRAF V600E mutation status by immunohistochemistry with a mutation-specific monoclonal antibody. Acta Neuropathol. 122, 11-19 (2011).
7. Marschall, A. L. J., Frenzel, A., Schirrmann, T., Schüngel, M. & Dubel, S. Targeting antibodies to the cytoplasm. mAbs 3, 3-16 (2011).
8. Rondon, I. J., & Marasco, A. W. Intracellular antibodies (intrabodies) for gene therapy of infectious diseases. Ann. Rev. Microbiol. 51, 257-283 (1997).
9. Kodadek, T., Reddy, M. M., Olivos, H. J., Bachhawat-Sikder, K. & Alluri, P. G. Synthetic molecules as antibody replacements. Acc. Chem. Res. 37, 711-718 (2004).
10. Testa, J. R. & Tsichlis, P. N. AKT signaling in normal and malignant cells. Oncogene 24, 7391-7393 (2005).
11. Vivanco, I. & Sawyers, C. L. The phosphatidylinositol 3-kinase-AKT pathway in human cancer. Nature Rev. Cancer 2, 489-501 (2002).
12. Carpten, J. D. et al. A transforming mutation in the pleckstrin homology domain of AKT1 in cancer. Nature 448, 439-444 (2007).
13. Nag, A. et al. A chemical epitope-targeting strategy for protein capture agents: the serine 474 epitope of the kinase Akt2. Angew. Chem. Int. Ed. 52, 13975-13979 (2013).
14. Agnew, H. D. et al. Iterative in situ click chemistry creates antibody-like proteincapture agents. Angew. Chem. Int. Ed. 48, 4944-4948 (2009).
15. Farrow, B. et al. A chemically synthesized capture agent enables the selective, sensitive, and robust electrochemical detection of anthrax protective antigen. ACS Nano 7, 9452-9660 (2013).
16. Millward, S. W. et al. Iterative in situ click chemistry assembles a branched capture agent and allosteric inhibitor for Akt1. J. Am. Chem. Soc. 133, 18280-18288 (2011).
17. Pfeilsticker, J. A. et al. A cocktail of thermally stable, chemically synthesized capture agents for the efficient detection of anti-Gp41 antibodies from human sera. PLoS ONE 8, e76224 (2013).
18. Millward, S. W. et al. In situ click chemistry: from small molecule discovery to synthetic antibodies. Integr. Biol. 5, 87-95 (2013).
19. Coin, I., Beyermann, M. & Bienert, M. Solid-phase peptide synthesis: from standard procedures to the synthesis of difficult sequences. Nature Protocols 2, 3247-3256 (2007).
20. Pashkova, A., Moskovets, E. & Karger, B. L. Coumarin tags for improved analysis of peptides by MALDI-TOF MS and MS/MS. 1. Enhancement in MALDI MS signal intensities. Anal. Chem. 76, 4550-4557 (2004).
21. Tsukiji, S., Miyagawa, M., Takaoka, Y., Tamura, T. & Hamachi, I. Liganddirected tosyl chemistry for protein labeling in vivo. Nature Chem. Biol. 5, 341-343 (2009).
22. Deshayes, S., Morris, M. C., Divita, G. & Heitz, F. Cell-penetrating peptides: tools for intracellular delivery of therapeutics. Cell. Mol. Life Sci. 62, 1839-1849 (2005).
23. Dunn, K.W., Kamocka, M. M. & McDonald, J. H. A practical guide to evaluating colocalization in biological microscopy. Am. J. Physiol. Cell Physiol. 300, C723-C742 (2011).
24. Mahadevan, D. et al. Discovery of a novel class of AKT pleckstrin homology domain inhibitors. Mol. Cancer Ther. 7, 2621-2632 (2008).
25. Hiromura, M. et al. Inhibition of Akt kinase activity by a peptide spanning the ?A strand of the proto-oncogene TCL1. J. Biol. Chem. 279, 53407-53418 (2004).
26. Verdine, G. L. & Hilinski, G. J. Stapled peptides for intracellular drug targets. Methods Enzymol. 503, 3-33 (2012).
27. Lee, S. S. et al. Accurate MALDI-TOF/TOF sequencing of one-bead-onecompound peptide libraries with application to the identification of multiligand protein affinity agents using in situ click chemistry screening. Anal. Chem. 82, 672-679 (2010).