First-in-class small molecule inhibitors of the single-strand DNA cytosine deaminase APOBEC3G

ACS Chemical Biology

Volumn 7, Issue 3, 2012, Pages 506-517

  Li, Ming ^a   Shandilya, Shivender M D ^b   Carpenter, Michael A ^a   Rathore, Anurag ^a   Brown, William L ^a   Perkins, Angela L ^d   Harki, Daniel A ^d   Solberg, Jonathan ^d   Hook, Derek J ^d   Pandey, Krishan K ^e   Parniak, Michael A ^f   Johnson, Jeffrey R ^g   Krogan, Nevan J ^g   Somasundaran, Mohan ^c   Ali, Akbar ^b   Schiffer, Celia A ^b   Harris, Reuben S ^a  

^a UNIVERSITY OF MINNESOTA   (United States)

^b UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

^c UNIVERSITY OF MASSACHUSETTS   (United States)

^d UNIVERSITY OF MINNESOTA   (United States)

^e SAINT LOUIS UNIVERSITY   (United States)

^f UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^g UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1,4 BENZOQUINONE; 2 AMINO 6,7 DIHYDROXY 1,2,3,4 TETRAHYDRONAPHTHALENE HYDROBROMIDE; 2,10,11 TRIHYDROXY N PROPYL NORAPORPHINE HYDROBROMIDE; 2,10,11 TRIHYDROXYAPORPHINE HYDROBROMIDE; 2,3,4,5 TETRAHYDRO 7,8 DIHYDROXY 1 PHENYL 1H 3 BENZAZEPINE; 3,4 DIHYDROXYPHENYLACETIC ACID; 4 CHLOROMERCURIBENZOIC ACID; APOMORPHINE HEMIHYDRATE; AURINTRICARBOXYLIC ACID; CAFFEIC ACID; CARBIDOPA; CATECHOL; CEFAPIRIN; CYTOSINE DEAMINASE; DEPHOSTATIN; DIHYDREXIDINE; EBSELEN; ENZYME INHIBITOR; GUANIDINONALTRINDOLE DI(TRIFLUOROACETATE); INTEGRASE; IODOACETAMIDE; N (2,3 DIPHENYL 1,2,4 THIADIAZOL 5(2H) YLIDENE)METHANAMINE; N ACETYLDOPAMINE MONOHYDRATE; N ALLYLNORAPOMORPHINE HYDROBROMIDE; PROPYLNORAPOMORPHINE; QUINONE DERIVATIVE; RIBONUCLEASE; SINGLE STRANDED DNA; SINGLE STRANDED DNA CYTOSINE DEAMINASE APOBEC3G INHIBITOR; SKF 89626; UNCLASSIFIED DRUG; UNINDEXED DRUG; URACIL DNA GLYCOSIDASE;

ARTICLE; BINDING SITE; CATALYSIS; DRUG IDENTIFICATION; DRUG PROTEIN BINDING; DRUG STRUCTURE; ENZYME ACTIVITY; ESCHERICHIA COLI; HIGH THROUGHPUT SCREENING; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; MASS SPECTROMETRY; MOLECULAR SIZE; NONHUMAN; OXIDATION KINETICS; PRIORITY JOURNAL; SUBSTITUTION REACTION;

CELLS, CULTURED; CRYSTALLOGRAPHY, X-RAY; CYTIDINE DEAMINASE; DOSE-RESPONSE RELATIONSHIP, DRUG; ENZYME ACTIVATION; ENZYME INHIBITORS; HEK293 CELLS; HIV INTEGRASE; HUMANS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; RIBONUCLEASE H; SMALL MOLECULE LIBRARIES; STRUCTURE-ACTIVITY RELATIONSHIP;

HUMAN IMMUNODEFICIENCY VIRUS 1; MAMMALIA;

EID: 84863368426     PISSN: 15548929     EISSN: 15548937     Source Type: Journal    
DOI: 10.1021/cb200440y     Document Type: Article

References (61)

1. Albin, J. S. and Harris, R. S. (2010) Interactions of host APOBEC3 restriction factors with HIV-1 in vivo: implications for therapeutics Expert Rev. Mol. Med. 12, e4
2. Malim, M. H. (2009) APOBEC proteins and intrinsic resistance to HIV-1 infection Philos. Trans. R. Soc., B 364, 675-687
3. Smith, J. L., Bu, W., Burdick, R. C., and Pathak, V. K. (2009) Multiple ways of targeting APOBEC3-virion infectivity factor interactions for anti-HIV-1 drug development Trends Pharmacol. Sci. 30, 638-646
4. Bishop, K. N., Verma, M., Kim, E. Y., Wolinsky, S. M., and Malim, M. H. (2008) APOBEC3G inhibits elongation of HIV-1 reverse transcripts PLoS Pathog. 4, e1000231
5. Schumacher, A. J., Haché, G., MacDuff, D. A., Brown, W. L., and Harris, R. S. (2008) The DNA deaminase activity of human APOBEC3G is required for Ty1, MusD, and human immunodeficiency virus type 1 restriction J. Virol. 82, 2652-2660 (Pubitemid 351329156)
6. Miyagi, E., Opi, S., Takeuchi, H., Khan, M., Goila-Gaur, R., Kao, S., and Strebel, K. (2007) Enzymatically active APOBEC3G is required for efficient inhibition of human immunodeficiency virus type 1 J. Virol. 81, 13346-13353 (Pubitemid 350247831)
7. Browne, E. P., Allers, C., and Landau, N. R. (2009) Restriction of HIV-1 by APOBEC3G is cytidine deaminase-dependent Virology 387, 313-321
8. Yu, X., Yu, Y., Liu, B., Luo, K., Kong, W., Mao, P., and Yu, X. F. (2003) Induction of APOBEC3G ubiquitination and degradation by an HIV-1 Vif-Cul5-SCF complex Science 302, 1056-1060 (Pubitemid 37386201)
9. LaRue, R. S., Lengyel, J., Jónsson, S. R., Andrésdó ttir, V., and Harris, R. S. (2010) Lentiviral Vif degrades the APOBEC3Z3/APOBEC3H protein of its mammalian host and is capable of cross-species activity J. Virol. 84, 8193-8201
10. Münk, C., Beck, T., Zielonka, J., Hotz-Wagenblatt, A., Chareza, S., Battenberg, M., Thielebein, J., Cichutek, K., Bravo, I. G., OBrien, S. J., Löchelt, M., and Yuhki, N. (2008) Functions, structure, and read-through alternative splicing of feline APOBEC3 genes Genome Biol. 9, R48
11. Bogerd, H. P., Tallmadge, R. L., Oaks, J. L., Carpenter, S., and Cullen, B. R. (2008) Equine infectious anemia virus resists the antiretroviral activity of equine APOBEC3 proteins through a packaging-independent mechanism J. Virol. 82, 11889-11901
12. Schmitt, K., Hill, M. S., Liu, Z., Ruiz, A., Culley, N., Pinson, D. M., and Stephens, E. B. (2010) Comparison of the replication and persistence of simian-human immunodeficiency viruses expressing Vif proteins with mutation of the SLQYLA or HCCH domains in macaques Virology 404, 187-203
13. Chen, K. M., Harjes, E., Gross, P. J., Fahmy, A., Lu, Y., Shindo, K., Harris, R. S., and Matsuo, H. (2008) Structure of the DNA deaminase domain of the HIV-1 restriction factor APOBEC3G Nature 452, 116-119 (Pubitemid 351355093)
14. Furukawa, A., Nagata, T., Matsugami, A., Habu, Y., Sugiyama, R., Hayashi, F., Kobayashi, N., Yokoyama, S., Takaku, H., and Katahira, M. (2009) Structure, interaction and real-time monitoring of the enzymatic reaction of wild-type APOBEC3G EMBO J. 28, 440-451
15. Harjes, E., Gross, P. J., Chen, K. M., Lu, Y., Shindo, K., Nowarski, R., Gross, J. D., Kotler, M., Harris, R. S., and Matsuo, H. (2009) An extended structure of the APOBEC3G catalytic domain suggests a unique holoenzyme model J. Mol. Biol. 389, 819-832
16. Holden, L. G., Prochnow, C., Chang, Y. P., Bransteitter, R., Chelico, L., Sen, U., Stevens, R. C., Goodman, M. F., and Chen, X. S. (2008) Crystal structure of the anti-viral APOBEC3G catalytic domain and functional implications Nature 456, 121-124
17. Shandilya, S. M. D., Nalam, M. N. L., Nalivaika, E. A., Gross, P. J., Valesano, J. C., Shindo, K., Li, M., Munson, M., Royer, W. E., Harjes, E., Kouno, T., Matsuo, H., Harris, R. S., Somasundaran, M., and Schiffer, C. A. (2010) Crystal structure of the APOBEC3G catalytic domain reveals potential oligomerization interfaces Structure 18, 28-38
18. LaRue, R. S., Andresdottir, V., Blanchard, Y., Conticello, S. G., Derse, D., Emerman, M., Greene, W. C., Jonsson, S. R., Landau, N. R., Lochelt, M., Malik, H. S., Malim, M. H., Munk, C., OBrien, S. J., Pathak, V. K., Strebel, K., Wain-Hobson, S., Yu, X. F., Yuhki, N., and Harris, R. S. (2009) Guidelines for naming nonprimate APOBEC3 genes and proteins J. Virol. 83, 494-497
19. Xiao, Z., Ehrlich, E., Luo, K., Xiong, Y., and Yu, X. F. (2007) Zinc chelation inhibits HIV Vif activity and liberates antiviral function of the cytidine deaminase APOBEC3G FASEB J. 21, 217-222 (Pubitemid 46052559)
20. Nathans, R., Cao, H., Sharova, N., Ali, A., Sharkey, M., Stranska, R., Stevenson, M., and Rana, T. M. (2008) Small-molecule inhibition of HIV-1 Vif Nat. Biotechnol. 26, 1187-1192
21. Cen, S., Peng, Z. G., Li, X. Y., Li, Z. R., Ma, J., Wang, Y. M., Fan, B., You, X. F., Wang, Y. P., Liu, F., Shao, R. G., Zhao, L. X., Yu, L., and Jiang, J. D. (2010) Small molecular inhibitors for HIV-1 replication through specifically stabilizing APOBEC3G J. Biol. Chem. 285, 16546-16552
22. Ejima, T., Hirota, M., Mizukami, T., Otsuka, M., and Fujita, M. (2011) An anti-HIV-1 compound that increases steady-state expression of apoplipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G Int. J. Mol. Med. 28, 613-616
23. Harris, R. S. (2008) Enhancing immunity to HIV through APOBEC Nat. Biotechnol. 26, 1089-1090
24. Haché, G., Mansky, L. M., and Harris, R. S. (2006) Human APOBEC3 proteins, retrovirus restriction, and HIV drug resistance AIDS Rev. 8, 148-157 (Pubitemid 44614032)
25. Sadler, H. A., Stenglein, M. D., Harris, R. S., and Mansky, L. M. (2010) APOBEC3G contributes to HIV-1 variation through sublethal mutagenesis J. Virol. 84, 7396-7404
26. Thielen, B. K., Klein, K. C., Walker, L. W., Rieck, M., Buckner, J. H., Tomblingson, G. W., and Lingappa, J. R. (2007) T cells contain an RNase-insensitive inhibitor of APOBEC3G deaminase activity PLoS Pathog. 3, 1320-1334 (Pubitemid 47510284)
27. Stenglein, M. D., Burns, M. B., Li, M., Lengyel, J., and Harris, R. S. (2010) APOBEC3 proteins mediate the clearance of foreign DNA from human cells Nat. Struct. Mol. Biol. 17, 222-229
28. Shlyakhtenko, L. S., Lushnikov, A. Y., Li, M., Lackey, L., Harris, R. S., and Lyubchenko, Y. L. (2011) Atomic force microscopy studies provide direct evidence for dimerization of the HIV restriction factor APOBEC3G J. Biol. Chem. 286, 3387-3395
29. Kim, B. H., Jee, J. G., Yin, C. H., Sandoval, C., Jayabose, S., Kitamura, D., Bach, E. A., and Baeg, G. H. (2010) NSC114792, a novel small molecule identified through structure-based computational database screening, selectively inhibits JAK3 Mol. Cancer 9, 36
30. Caffrey, D. R., Lunney, E. A., and Moshinsky, D. J. (2008) Prediction of specificity-determining residues for small-molecule kinase inhibitors BMC Bioinformatics 9, 491
31. Fedorov, O., Marsden, B., Pogacic, V., Rellos, P., Muller, S., Bullock, A. N., Schwaller, J., Sundstrom, M., and Knapp, S. (2007) A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases Proc. Natl. Acad. Sci. U.S.A. 104, 20523-20528
32. Fischer, P. M. (2004) The design of drug candidate molecules as selective inhibitors of therapeutically relevant protein kinases Curr. Med. Chem. 11, 1563-1583 (Pubitemid 38735797)
33. Benchokroun, Y., Couprie, J., and Larsen, A. K. (1995) Aurintricarboxylic acid, a putative inhibitor of apoptosis, is a potent inhibitor of DNA topoisomerase II in vitro and in Chinese hamster fibrosarcoma cells Biochem. Pharmacol. 49, 305-313
34. Gonzalez, R. G., Haxo, R. S., and Schleich, T. (1980) Mechanism of action of polymeric aurintricarboxylic acid, a potent inhibitor of protein - nucleic acid interactions Biochemistry 19, 4299-4303
35. Hashem, A. M., Flaman, A. S., Farnsworth, A., Brown, E. G., Van Domselaar, G., He, R., and Li, X. (2009) Aurintricarboxylic acid is a potent inhibitor of influenza A and B virus neuraminidases PloS One 4, e8350
36. Bak, A., Magdziarz, T., Kurczyk, A., and Polanski, J. (2011) Mapping drug architecture by MoStBioDat: Rapid screening of intramolecular hydrogen bonded motifs in catechols Drug Dev. Res. 72, 209-218
37. Iwatani, Y., Takeuchi, H., Strebel, K., and Levin, J. G. (2006) Biochemical activities of highly purified, catalytically active human APOBEC3G: correlation with antiviral effect J. Virol. 80, 5992-6002 (Pubitemid 43849177)
38. Chelico, L., Pham, P., Calabrese, P., and Goodman, M. F. (2006) APOBEC3G DNA deaminase acts processively 3′ → 5′ on single-stranded DNA Nat. Struct. Mol. Biol. 13, 392-399 (Pubitemid 43881578)
39. Nowarski, R., Britan-Rosich, E., Shiloach, T., and Kotler, M. (2008) Hypermutation by intersegmental transfer of APOBEC3G cytidine deaminase Nat. Struct. Mol. Biol. 15, 1059-1066
40. Demorest, Z. L., Li, M., and Harris, R. S. (2011) Phosphorylation directly regulates the intrinsic DNA cytidine deaminase activity of activation-induced deaminase and APOBEC3G protein J. Biol. Chem. 286, 26568-26575
41. McDougall, W. M., Okany, C., and Smith, H. C. (2011) Deaminase activity on ssDNA occurred in vitro when APOBEC3G forms homotetramers and higher-order complexes J. Biol. Chem. 286, 30655-30661
42. Schweigert, N., Zehnder, A. J., and Eggen, R. I. (2001) Chemical properties of catechols and their molecular modes of toxic action in cells, from microorganisms to mammals Environ. Microbiol. 3, 81-91 (Pubitemid 33141423)
43. Himmel, D. M., Sarafianos, S. G., Dharmasena, S., Hossain, M. M., McCoy-Simandle, K., Ilina, T., Clark, A. D., Jr., Knight, J. L., Julias, J. G., Clark, P. K., Krogh-Jespersen, K., Levy, R. M., Hughes, S. H., Parniak, M. A., and Arnold, E. (2006) HIV-1 reverse transcriptase structure with RNase H inhibitor dihydroxy benzoyl naphthyl hydrazone bound at a novel site ACS Chem. Biol. 1, 702-712
44. Fesen, M. R., Kohn, K. W., Leteurtre, F., and Pommier, Y. (1993) Inhibitors of human immunodeficiency virus integrase Proc. Natl. Acad. Sci. U.S.A. 90, 2399-2403 (Pubitemid 23078634)
45. Fesen, M. R., Pommier, Y., Leteurtre, F., Hiroguchi, S., Yung, J., and Kohn, K. W. (1994) Inhibition of HIV-1 integrase by flavones, caffeic acid phenethyl ester (CAPE) and related compounds Biochem. Pharmacol. 48, 595-608 (Pubitemid 24257024)
46. Crosby, D. C., Lei, X., Gibbs, C. G., McDougall, B. R., Robinson, W. E., and Reinecke, M. G. (2010) Design, synthesis, and biological evaluation of novel hybrid dicaffeoyltartaric/diketo acid and tetrazole-substituted L-chicoric acid analogue inhibitors of human immunodeficiency virus type 1 integrase J. Med. Chem. 53, 8161-8175
47. Gong, Q., Menon, L., Ilina, T., Miller, L. G., Ahn, J., Parniak, M. A., and Ishima, R. (2011) Interaction of HIV-1 reverse transcriptase ribonuclease H with an acylhydrazone inhibitor Chem. Biol. Drug Design 77, 39-47
48. Chung, S., Himmel, D. M., Jiang, J. K., Wojtak, K., Bauman, J. D., Rausch, J. W., Wilson, J. A., Beutler, J. A., Thomas, C. J., Arnold, E., and Le Grice, S. F. (2011) Synthesis, activity, and structural analysis of novel alpha-hydroxytropolone inhibitors of human immunodeficiency virus reverse transcriptase-associated ribonuclease H J. Med. Chem. 54, 4462-4473
49. Reinke, R. A., King, P. J., Victoria, J. G., McDougall, B. R., Ma, G., Mao, Y., Reinecke, M. G., and Robinson, W. E., Jr. (2002) Dicaffeoyltartaric acid analogues inhibit human immunodeficiency virus type 1 (HIV-1) integrase and HIV-1 replication at nontoxic concentrations J. Med. Chem. 45, 3669-3683 (Pubitemid 34856107)
50. Robinson, W. E., Jr., Cordeiro, M., Abdel-Malek, S., Jia, Q., Chow, S. A., Reinecke, M. G., and Mitchell, W. M. (1996) Dicaffeoylquinic acid inhibitors of human immunodeficiency virus integrase: inhibition of the core catalytic domain of human immunodeficiency virus integrase Mol. Pharmacol. 50, 846-855 (Pubitemid 26347704)
51. King, P. J., Ma, G., Miao, W., Jia, Q., McDougall, B. R., Reinecke, M. G., Cornell, C., Kuan, J., Kim, T. R., and Robinson, W. E., Jr. (1999) Structure-activity relationships: analogues of the dicaffeoylquinic and dicaffeoyltartaric acids as potent inhibitors of human immunodeficiency virus type 1 integrase and replication J. Med. Chem. 42, 497-509 (Pubitemid 29085110)
52. Pandey, K. K., Bera, S., Vora, A. C., and Grandgenett, D. P. (2010) Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors Biochemistry 49, 8376-8387
53. Imoto, M., Kakeya, H., Sawa, T., Hayashi, C., Hamada, M., Takeuchi, T., and Umezawa, K. (1993) Dephostatin, a novel protein tyrosine phosphatase inhibitor produced by Streptomyces. I. Taxonomy, isolation, and characterization J. Antibiot. (Tokyo) 46, 1342-1346 (Pubitemid 23290981)
54. Kakeya, H., Imoto, M., Takahashi, Y., Naganawa, H., Takeuchi, T., and Umezawa, K. (1993) Dephostatin, a novel protein tyrosine phosphatase inhibitor produced by Streptomyces. II. Structure determination J. Antibiot. (Tokyo) 46, 1716-1719 (Pubitemid 23355458)
55. Uesugi, Y., Fuse, I., Toba, K., Kishi, K., Hashimoto, S., Furukawa, T., Narita, M., Takahashi, M., and Aizawa, Y. (2000) Inhibition of ATRA-induced myeloid differentiation in acute promyelocytic leukemia by a new protein tyrosine phosphatase inhibitor, 3,4-dephostatin J. Exp. Clin. Cancer Res. 19, 363-366
56. Watanabe, T., Suzuki, T., Umezawa, Y., Takeuchi, T., Otsuka, M., and Umezawa, K. (2000) Structure-activity relationship and rational design of 3,4-dephostatin derivatives as protein tyrosine phosphatase inhibitors Tetrahedron 56, 741-752 (Pubitemid 30077969)
57. Watanabe, T., Takeuchi, T., Otsuka, M., Tanaka, S., and Umezawa, K. (1995) Synthesis and protein tyrosine phosphatase inhibitory activity of dephostatin analogs J. Antibiot. (Tokyo) 48, 1460-1466 (Pubitemid 26016906)
58. Umezawa, K., Kawakami, M., and Watanabe, T. (2003) Molecular design and biological activities of protein-tyrosine phosphatase inhibitors Pharmacol. Ther. 99, 15-24 (Pubitemid 36694747)
59. Hellman, U., Wernstedt, C., Gonez, J., and Heldin, C. H. (1995) Improvement of an "In-Gel" digestion procedure for the micropreparation of internal protein fragments for amino acid sequencing Anal. Biochem. 224, 451-455
60. Rosenfeld, J., Capdevielle, J., Guillemot, J. C., and Ferrara, P. (1992) In-gel digestion of proteins for internal sequence analysis after one- or two-dimensional gel electrophoresis Anal. Biochem. 203, 173-179
61. Clauser, K. R., Baker, P., and Burlingame, A. L. (1999) Role of accurate mass measurement (α10 ppm) in protein identification strategies employing MS or MS/MS and database searching Anal. Chem. 71, 2871-2882 (Pubitemid 29340480)