Structure-activity relationships in human toll-like receptor 2-specific monoacyl lipopeptides

Journal of Medicinal Chemistry

Volumn 55, Issue 7, 2012, Pages 3353-3363

  Salunke, Deepak B ^a   Shukla, Nikunj M ^a   Yoo, Euna ^a   Crall, Breanna M ^a   Balakrishna, Rajalakshmi ^a   Malladi, Subbalakshmi S ^a   David, Sunil A ^a  

^a UNIVERSITY OF KANSAS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 (DITETRADECYLAMINO)ACETIC ACID; 2 [(TERT BUTOXYCARBONYL)(TETRADECYL)AMINO]ACETIC ACID; 2 [[ 3 [[3 (TERT BUTOXY) 1 METHOXY 1 OXOPROPAN 2 YL] AMINO] 2 [(TERT BUTOXYCARBONYL) AMINO] 3 OXOPROPYL]THIO]ETHYL [1,1' BIPHENYL] 3 CARBOXYLATE; 2 [[2 (ETHYLAMINO) 3 [(3 HYDROXY 1 METHOXY 1 OXOPROPAN 2 YL)AMINO] 3 OXOPROPYL]THIO]ETHYL PALMITATE; 2 [[2 (HEXADECYLAMINO) 3 [(3 HYDROXY 1 METHOXY 1 OXOPROPAN 2 YL)AMINO] 3 OXOPROPYL]THIO]ETHYL PALMITATE; 2 [[2 ACETAMIDO 3 [(3 HYDROXY 1 METHOXY 1 OXOPROPAN 2 YL)AMINO] 3 OXOPROPYL]THIO]ETHYL PALMITATE; 2 [[2 AMINO 3 [(3 HYDROXY 1 METHOXY 1 OXOPROPAN 2 YL)AMINO] 3 OXOPROPYL]THIO]ETHYL [1,1' BIPHENYL] 4 CARBOXYLATE; 2 [[2 AMINO 3 [(3 HYDROXY 1 METHOXY 1 OXOPROPAN 2 YL)AMINO] 3 OXOPROPYL]THIO]ETHYL BUTYRATE; 2 [[2 AMINO 3 [(3 HYDROXY 1 METHOXY 1 OXOPROPAN 2 YL)AMINO] 3 OXOPROPYL]THIO]ETHYL DODECANOATE; 2 [[2 AMINO 3 [(3 HYDROXY 1 METHOXY 1 OXOPROPAN 2 YL)AMINO] 3 OXOPROPYL]THIO]ETHYL OCTANOATE; 2 [[2 AMINO 3 [(3 HYDROXY 1 METHOXY 1 OXOPROPAN 2 YL)AMINO] 3 OXOPROPYL]THIO]ETHYL STEARATE; 2 [[2 AMINO 3 [(3 HYDROXY 1 METHOXY 1 OXOPROPAN 2 YL)AMINO] 3 OXOPROPYL]THIO]ETHYL[1,1' BIPHENYL] 3 CARBOXYLATE; 2 [[3 [(3 HYDROXY 1 METHOXY 1 OXOPROPAN 2 YL)AMINO] 2 (METHYLSULFONAMIDO) 3 OXO PROPYL]THIO]ETHYL PALMITATE; 2 [[3 [(3 HYDROXY 1 METHOXY 1 OXOPROPAN 2 YL)AMINO] 2 (OCTYLAMINO) 3 OXOPROPYL]THIO]ETHYL PALMITATE; 2 [[3 [(3 HYDROXY 1 METHOXY 1 OXOPROPAN 2 YL)AMINO] 3 OXO 2 (2,2,2 TRIFLUORO ACETAMIDO)PROPYL]THIO]ETHYL PALMITATE; 2 [[3 [(3 HYDROXY 1 METHOXY 1 OXOPROPAN 2 YL)AMINO] 3 OXO 2 (TRIFLUOROMETHYL SULFONAMIDO)PROPYL]THIO]ETHYL PALMITATE; 2 [[3 [[3 (TERT BUTOXY) 1 METHOXY 1 OXOPROPAN 2 YL] AMINO] 2 [(TERT BUTOXYCARBONYL) AMINO] 3 OXOPROPYL]THIO]ETHYL [1,1' BIPHENYL] 4 CARBOXYLATE; 2 [[3 [[3 (TERT BUTOXY) 1 METHOXY 1 OXOPROPAN 2 YL] AMINO] 2 [(TERT BUTOXYCARBONYL) AMINO] 3 OXOPROPYL]THIO]ETHYL DODECANOATE; 2 [[3 [[3 (TERT BUTOXY) 1 METHOXY 1 OXOPROPAN 2 YL] AMINO] 2 [(TERT BUTOXYCARBONYL) AMINO] 3 OXOPROPYL]THIO]ETHYL OCTANOATE; 2 [[3 [[3 (TERT BUTOXY) 1 METHOXY 1 OXOPROPAN 2 YL] AMINO] 2 [(TERT BUTOXYCARBONYL) AMINO] 3 OXOPROPYL]THIO]ETHYL STEARATE; 2 [[3 [[3 (TERT BUTOXY) 1 METHOXY 1 OXOPROPAN 2 YL]AMINO] 2 [(TERT BUTOXYCARBONYL) AMINO] 3 OXOPROPYL]THIO]ETHYL BUTYRATE; 3 [[2 ACETAMIDO 3 [(3 HYDROXY 1 METHOXY 1 OXOPROPAN 2 YL)AMINO] 3 OXOPROPYL]THIO]PROPYL PALMITATE; LIPOPEPTIDE; METHYL 2 (DITETRADECYLAMINO)ACETATE; METHYL 2 [(TERT BUTOXYCARBONYL)(TETRADECYL)AMINO]ACETATE; METHYL 2 [2 AMINO 3 [[2 (2 (DITETRADECYLAMINO)ACETOXY]ETHYL]THIO]PROPAN AMIDO] 3 HYDROXYPROPANOATE HYDROXYPROPANOATE; METHYL 2 [2 AMINO 3 [[2 [2 (TETRADECYLAMINO)ACETOXY]ETHYL]THIO]PROPANAMIDO] 3 HYDROXYPROPANOATE; TOLL LIKE RECEPTOR 2; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANIMAL CELL; ARTICLE; CONTROLLED STUDY; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; HUMAN CELL; NONHUMAN; STRUCTURE ACTIVITY RELATION;

ADJUVANTS, IMMUNOLOGIC; ANIMALS; DIPEPTIDES; GENES, REPORTER; HEK293 CELLS; HUMANS; LIPOPEPTIDES; LIPOPROTEINS; MICE; NF-KAPPA B; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; TOLL-LIKE RECEPTOR 2;

EID: 84859802144     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm3000533     Document Type: Article

References (37)

1. Hilleman, M. R. Vaccines in historic evolution and perspective: a narrative of vaccine discoveries Vaccine 2000, 18, 1436-1447
2. Pashine, A.; Valiante, N. M.; Ulmer, J. B. Targeting the innate immune response with improved vaccine adjuvants Nature Med. 2005, 11, S63-S68
3. Glenny, A. T.; Pope, C. G.; Waddington, H.; Wallace, V. The antigenic value of toxoid precipitated by potassium-alum J. Pathol. Bacteriol. 1926, 29, 38-45
4. Vogel, F. R.; Powell, M. F. A compendium of vaccine adjuvants and excipients Pharm. Biotechnol. 1995, 6, 141-228
5. Garcon, N.; Van Mechelen, M. Recent clinical experience with vaccines using MPL- and QS-21-containing adjuvant systems Expert. Rev. Vaccines 2011, 10, 471-486
6. Relyveld, E. H.; Bizzini, B.; Gupta, R. K. Rational approaches to reduce adverse reactions in man to vaccines containing tetanus and diphtheria toxoids Vaccine 1998, 16, 1016-1023
7. Gupta, R. K. Aluminum compounds as vaccine adjuvants Adv. Drug Delivery Rev. 1998, 32, 155-172
8. Kawai, T.; Akira, S. TLR signaling Semin. Immunol. 2007, 19, 24-32
9. Kumagai, Y.; Takeuchi, O.; Akira, S. Pathogen recognition by innate receptors J. Infect. Chemother. 2008, 14, 86-92
10. Kumagai, Y.; Takeuchi, O.; Akira, S. Pathogen recognition by innate receptors J. Infect. Chemother. 2008, 14, 86-92
11. Takeda, K.; Akira, S. Toll-like receptors. Curr. Protoc. Immunol. 2007, Chapter 14, Unit 14, p 12.
12. Akira, S. Toll-like receptors and innate immunity Adv. Immunol. 1902, 78, 1-56
13. Akira, S.; Takeda, K.; Kaisho, T. Toll-like receptors: critical proteins linking innate and acquired immunity Nature Immunol. 2001, 2, 675-680
14. Cottalorda, A.; Verschelde, C.; Marcais, A.; Tomkowiak, M.; Musette, P.; Uematsu, S.; Akira, S.; Marvel, J.; Bonnefoy-Berard, N. TLR2 engagement on CD8 T cells lowers the threshold for optimal antigen-induced T cell activation Eur. J. Immunol. 2006, 36, 1684-1693
15. Kaisho, T.; Akira, S. Toll-like receptors as adjuvant receptors Biochim. Biophys. Acta 2002, 1589, 1-13
16. Agnihotri, G.; Ukani, R.; Malladi, S. S.; Warshakoon, H. J.; Balakrishna, R.; Wang, X.; David, S. A. Structure-activity relationships in nucleotide oligomerization domain 1 (Nod1) agonistic gamma-glutamyldiaminopimelic acid derivatives J. Med. Chem. 2011, 54, 1490-1510
17. Agnihotri, G.; Crall, B. M.; Lewis, T. C.; Day, T. P.; Balakrishna, R.; Warshakoon, H. J.; Malladi, S. S.; David, S. A. Structure-activity relationships in toll-like receptor 2-agonists leading to simplified monoacyl lipopeptides J. Med. Chem. 2011, 54, 8148-8160
18. Kimbrell, M. R.; Warshakoon, H.; Cromer, J. R.; Malladi, S.; Hood, J. D.; Balakrishna, R.; Scholdberg, T. A.; David, S. A. Comparison of the immunostimulatory and proinflammatory activities of candidate Gram-positive endotoxins, lipoteichoic acid, peptidoglycan, and lipopeptides, in murine and human cells Immunol. Lett. 2008, 118, 132-141
19. Shukla, N. M.; Kimbrell, M. R.; Malladi, S. S.; David, S. A. Regioisomerism-dependent TLR7 agonism and antagonism in an imidazoquinoline Bioorg. Med. Chem. Lett. 2009, 19, 2211-2214
20. Shukla, N. M.; Malladi, S. S.; Mutz, C. A.; Balakrishna, R.; David, S. A. Structure-activity relationships in human toll-like receptor 7-active imidazoquinoline analogues J. Med. Chem. 2010, 53, 4450-4465
21. Shukla, N. M.; Lewis, T. C.; Day, T. P.; Mutz, C. A.; Ukani, R.; Hamilton, C. D.; Balakrishna, R.; David, S. A. Toward self-adjuvanting subunit vaccines: model peptide and protein antigens incorporating covalently bound toll-like receptor-7 agonistic imidazoquinolines Bioorg. Med. Chem. Lett. 2011, 21, 3232-3236
22. Warshakoon, H. J.; Hood, J. D.; Kimbrell, M. R.; Malladi, S.; Wu, W. Y.; Shukla, N. M.; Agnihotri, G.; Sil, D.; David, S. A. Potential adjuvantic properties of innate immune stimuli Hum. Vaccines 2009, 5, 381-394
23. Wu, W.; Li, R.; Malladi, S. S.; Warshakoon, H. J.; Kimbrell, M. R.; Amolins, M. W.; Ukani, R.; Datta, A.; David, S. A. Structure-activity relationships in toll-like receptor-2 agonistic diacylthioglycerol lipopeptides J. Med. Chem. 2010, 53, 3198-3213
24. Ukani, R.; Lewis, T. C.; Day, T. P.; Wu, W.; Malladi, S. S.; Warshakoon, H. J.; David, S. A. Potent adjuvantic activity of a CCR1-agonistic bis-quinoline Bioorg. Med. Chem. Lett. 2012, 22, 293-295
25. Hood, J. D.; Warshakoon, H. J.; Kimbrell, M. R.; Shukla, N. M.; Malladi, S.; Wang, X.; David, S. A. Immunoprofiling toll-like receptor ligands: comparison of immunostimulatory and proinflammatory profiles in ex vivo human blood models Hum. Vaccines 2010, 6, 1-14
26. Jin, M. S.; Kim, S. E.; Heo, J. Y.; Lee, M. E.; Kim, H. M.; Paik, S. G.; Lee, H.; Lee, J. O. Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide Cell 2007, 130, 1071-1082
27. Kang, J. Y.; Lee, J. O. Structural biology of the Toll-like receptor family Annu. Rev. Biochem. 2011, 80, 917-941
28. Jin, M. S.; Lee, J. O. Structures of TLR-ligand complexes Curr. Opin. Immunol. 2008, 20, 414-419
29. Seyberth, T.; Voss, S.; Brock, R.; Wiesmuller, K. H.; Jung, G. Lipolanthionine peptides act as inhibitors of TLR2-mediated IL-8 secretion. Synthesis and structure-activity relationships J. Med. Chem. 2006, 49, 1754-1765
30. Kang, J. Y.; Nan, X.; Jin, M. S.; Youn, S. J.; Ryu, Y. H.; Mah, S.; Han, S. H.; Lee, H.; Paik, S. G.; Lee, J. O. Recognition of lipopeptide patterns by Toll-like receptor 2-Toll-like receptor 6 heterodimer Immunity 2009, 31, 873-884
31. Schroder, N. W.; Morath, S.; Alexander, C.; Hamann, L.; Hartung, T.; Zahringer, U.; Gobel, U. B.; Weber, J. R.; Schumann, R. R. Lipoteichoic acid (LTA) of Streptococcus pneumoniae and Staphylococcus aureus activates immune cells via Toll-like receptor (TLR)-2, lipopolysaccharide-binding protein (LBP), and CD14, whereas TLR-4 and MD-2 are not involved J. Biol. Chem. 2003, 278, 15587-15594
32. Stadelmaier, A.; Morath, S.; Hartung, T.; Schmidt, R. R. Synthesis of the first fully active lipoteichoic acid Angew. Chem., Int. Ed. Engl. 2003, 42, 916-920
33. Byrd-Leifer, C. A.; Block, E. F.; Takeda, K.; Akira, S.; Ding, A. The role of MyD88 and TLR4 in the LPS-mimetic activity of Taxol Eur. J. Immunol. 2001, 31, 2448-2457
34. Bryant, C. E.; Ouellette, A.; Lohmann, K.; Vandenplas, M.; Moore, J. N.; Maskell, D. J.; Farnfield, B. A. The cellular Toll-like receptor 4 antagonist E5531 can act as an agonist in horse whole blood Vet. Immunol. Immunopathol. 2007, 116, 182-189
35. Omueti, K. O.; Beyer, J. M.; Johnson, C. M.; Lyle, E. A.; Tapping, R. I. Domain exchange between human toll-like receptors 1 and 6 reveals a region required for lipopeptide discrimination J. Biol. Chem. 2005, 280, 36616-36625
36. Picard, C.; Puel, A.; Bonnet, M.; Ku, C. L.; Bustamante, J.; Yang, K.; Soudais, C.; Dupuis, S.; Feinberg, J.; Fieschi, C.; Elbim, C.; Hitchcock, R.; Lammas, D.; Davies, G.; Al Ghonaium, A.; Al Rayes, H.; Al Jumaah, S.; Al Hajjar, S.; Al Mohsen, I. Z.; Frayha, H. H.; Rucker, R.; Hawn, T. R.; Aderem, A.; Tufenkeji, H.; Haraguchi, S.; Day, N. K.; Good, R. A.; Gougerot-Pocidalo, M. A.; Ozinsky, A.; Casanova, J. L. Pyogenic bacterial infections in humans with IRAK-4 deficiency Science 2003, 299, 2076-2079
37. Shukla, N. M.; Malladi, S. S.; Day, V.; David, S. A. Preliminary evaluation of a 3H imidazoquinoline library as dual TLR7/TLR8 antagonists Bioorg. Med. Chem. 2011, 19, 3801-3811