A synthetic antimicrobial peptidomimetic (LTX 109): Stereochemical impact on membrane disruption

Journal of Medicinal Chemistry

Volumn 54, Issue 16, 2011, Pages 5786-5795

  Isaksson, Johan ^a   Brandsdal, Bjørn O ^a   Engqvist, Magnus ^b   Flaten, Gøril Eide ^a   Svendsen, John S Mjøen ^a,b   Stensen, Wenche ^b  

^a UNIVERSITY OF TROMSØ   (Norway)

^b LYTIX BIOPHARMA AS   (Norway)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIINFECTIVE AGENT; LTX 109; PEPTIDOMIMETIC AGENT; UNCLASSIFIED DRUG;

ANTIMICROBIAL ACTIVITY; AQUEOUS SOLUTION; ARTICLE; DRUG SYNTHESIS; ESCHERICHIA COLI; HYDROPHOBICITY; LIPID BILAYER; MEMBRANE DAMAGE; MOLECULAR DYNAMICS; NONHUMAN; NUCLEAR MAGNETIC RESONANCE; PHOSPHOLIPID BILAYER; PSEUDOMONAS AERUGINOSA; SOLUBILITY; STAPHYLOCOCCUS AUREUS; STEREOCHEMISTRY; STEREOISOMERISM; STRUCTURE ACTIVITY RELATION;

ANTIMICROBIAL CATIONIC PEPTIDES; CELL MEMBRANE; ESCHERICHIA COLI; GLYCEROPHOSPHOLIPIDS; HEMOLYSIS; HUMANS; HYDROPHOBIC AND HYDROPHILIC INTERACTIONS; LIPID BILAYERS; LIPOSOMES; MAGNETIC RESONANCE SPECTROSCOPY; MICROBIAL SENSITIVITY TESTS; MODELS, MOLECULAR; MOLECULAR DYNAMICS SIMULATION; MOLECULAR STRUCTURE; OLIGOPEPTIDES; PEPTIDOMIMETICS; PROTEIN CONFORMATION; PROTEIN STRUCTURE, SECONDARY; PSEUDOMONAS AERUGINOSA; SOLUTIONS; STAPHYLOCOCCUS AUREUS; STEREOISOMERISM;

EID: 80051860378     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm200450h     Document Type: Article

References (50)

1. Steiner, H.; Hultmark, D.; Engstrom, A.; Bennich, H.; Boman, H. G. Sequence and specificity of two antibacterial proteins involved in insect immunity Nature 1981, 292, 246-248 (Pubitemid 11001840)
2. Zasloff, M. Magainins, a class of antimicrobial peptides from xenopus skin - isolation, characterization of 2 active forms, and partial cDNA sequence of a precursor Proc. Natl. Acad. Sci. U.S.A. 1987, 84, 5449-5453 (Pubitemid 17129018)
3. Yang, L.; Weiss, T.; Lehrer, R.; Huang, H. Crystallization of antimicrobial pores in membranes: magainin and protegrin Biophys. J. 2000, 79, 2002-2009
4. Shai, Y. Mechanism of the binding, insertion and destabilization of phospholipid bilayer membranes by alpha-helical antimicrobial and cell non-selective membrane-lytic peptides Biochim. Biophys. Acta, Biomembr. 1999, 1462, 55-70
5. Matsuzaki, K. Why and how are peptide-lipid interactions utilized for self-defense? Magainins and tachyplesins as archetypes Biochim. Biophys. Acta, Biomembr. 1999, 1462, 1-10
6. Strömstedt, A. A.; Ringstad, L.; Schmidtchen, A.; Malmsten, M. Interaction between amphiphilic peptides and phospholipid membranes Curr. Opin. Colloid Interface Sci. 2010, 15, 467-478
7. Wimley, W.; Hristova, K. Antimicrobial peptides: successes, challenges and unanswered questions J. Membr. Biol. 2011, 239, 27-34
8. Haug, B. E.; Stensen, W.; Kalaaji, M.; Rekdal, O.; Svendsen, J. S. Synthetic antimicrobial peptidomimetics with therapeutic potential J. Med. Chem. 2008, 51, 4306-4314 (Pubitemid 352032455)
9. Hancock, R. E. W.; Sahl, H.-G. Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies Nat. Biotechnol. 2006, 24, 1551-1557 (Pubitemid 44967479)
10. Perron, G. G.; Zasloff, M.; Bell, G. Experimental evolution of resistance to an antimicrobial peptide Proc. R. Soc. B 2006, 273, 251-256 (Pubitemid 46768100)
11. Shafer, W. M.; Kraus, D.; Peschel, A. Molecular Mechanisms of Bacterial Resistance to Antimicrobial Peptides. In Antimicrobial Peptides and Human Disease; Springer: Berlin, Germany: 2006; Vol. 306, pp 231-250. (Pubitemid 47400324)
12. Ginsburg, I.; Koren, E. Are cationic antimicrobial peptides also "double-edged swords"? Expert Rev. Anti-Infect. Ther. 2008, 6, 453-462
13. Svenson, J.; Stensen, W.; Brandsdal, B. r.-O.; Haug, B. E.; Monrad, J.; Svendsen, J. S. Antimicrobial peptides with stability toward tryptic degradation Biochemistry 2008, 47, 3777-3788 (Pubitemid 351431368)
14. Karstad, R.; Isaksen, G.; Brandsdal, B. r.-O.; Svendsen, J. S.; Svenson, J. Unnatural amino acid side chains as S1, S1, and S2′ probes yield cationic antimicrobial peptides with stability toward chymotryptic degradation J. Med. Chem. 2010, 53, 5558-5566
15. Peschel, A.; Otto, M.; Jack, R. W.; Kalbacher, H.; Jung, G.; Götz, F. Inactivation of the dlt operon in Staphylococcus aureus confers sensitivity to defensins, protegrins, and other antimicrobial peptides J. Biol. Chem. 1999, 274, 8405-8410 (Pubitemid 29164628)
16. Weidenmaier, C.; Kristian, S. A.; Peschel, A. Bacterial resistance to antimicrobial host defenses - an emerging target for novel antiinfective strategies? Curr. Drug Targets 2003, 4, 643-649 (Pubitemid 37236379)
17. Frick, I.-M.; Kesson, P.; Rasmussen, M.; Schmidtchen, A.; Björck, L. SIC, a Secreted protein of Streptococcus pyogenes that inactivates antibacterial peptides J. Biol. Chem. 2003, 278, 16561-16566 (Pubitemid 36799517)
18. Jin, T.; Bokarewa, M.; Foster, T.; Mitchell, J.; Higgins, J.; Tarkowski, A. Staphylococcus aureus resists human defensins by production of staphylokinase, a novel bacterial evasion mechanism J. Immunol. 2004, 172, 1169-1176 (Pubitemid 38113778)
19. Borges-Walmsley, M. I.; McKeegan, K. S.; Walmsley, A. R. Structure and function of efflux pumps that confer resistance to drugs Biochem. J. 2003, 376, 313-338 (Pubitemid 38010517)
20. van Veen, H. W. Towards the molecular mechanism of prokaryotic and eukaryotic multidrug transporters Semin. Cell Dev. Biol. 2001, 12, 239-245
21. Shafer, W. M.; Qu, X.-D.; Waring, A. J.; Lehrer, R. I. Modulation of Neisseria gonorrhoeae susceptibility to vertebrate antibacterial peptides due to a member of the resistance/nodulation/division efflux pump family Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 1829-1833 (Pubitemid 28103479)
22. Perona, J. J.; Craik, C. S. Evolutionary divergence of substrate specificity within the chymotrypsin-like serine protease fold J. Biol. Chem. 1997, 272, 29987-29990 (Pubitemid 27512189)
23. Strom, M.; Rekdal, O.; Svendsen, J. Antibacterial activity of 15-residue lactoferricin derivatives J. Pept. Res. 2000, 56, 265-274
24. Strom, M.; Rekdal, O.; Stensen, W.; Svendsen, J. Increased antibacterial activity of 15-residue murine lactoferricin derivatives J. Pept. Res. 2001, 57, 127-139 (Pubitemid 32157800)
25. Strom, M.; Haug, B.; Skar, M.; Stensen, W.; Stiberg, T.; Svendsen, J. The pharmacophore of short cationic antibacterial peptides J. Med. Chem. 2003, 46, 1567-1570 (Pubitemid 36444211)
26. Haug, B. E.; Stensen, W.; Svendsen, J. S. Application of the Suzuki-Miyaura cross-coupling to increase antimicrobial potency generates promising novel antibacterials Bioorg. Med. Chem. Lett. 2007, 17, 2361-2364 (Pubitemid 46484291)
27. Haug, B.; Andersen, J.; Rekdal, O.; Svendsen, J. Synthesis of a 2-aryisulphonylated tryptophan: the antibacterial activity of bovine lactoferricin peptides containing Trp(2-Pmc) J. Pept. Sci. 2002, 8, 307-313 (Pubitemid 34784922)
28. Haug, B.; Skar, M.; Svendsen, J. Bulky aromatic amino acids increase the antibacterial activity of 15-residue bovine lactoferricin derivatives J. Pept. Sci. 2001, 7, 425-432 (Pubitemid 32782817)
29. Haug, B.; Stensen, W.; Stiberg, T.; Svendsen, J. Bulky nonproteinogenic amino acids permit the design of very small and effective cationic antibacterial peptides J. Med. Chem. 2004, 47, 4159-4162 (Pubitemid 39045422)
30. Amsterdam, D. Susceptibility Testing of Antimicrobials in Liquid Media. In Antibiotics in Laboratory Medicine, 4 th ed.; Lorian, V., Ed.; Williams and Wilkins Co: Baltimore, MD, 1996; pp 75-78.
31. Strøm, M. B.; Haug, B. E.; Skar, M. L.; Stensen, W.; Stiberg, T.; Svendsen, J. S. The pharmacophore of short cationic antibacterial peptides J. Med. Chem. 2003, 46, 1567-1570 (Pubitemid 36444211)
32. Brandl, M. Liposomes as drug carriers: a technological approach Biotechnol. Annu. Rev. 2001, 7, 59-85 (Pubitemid 41081525)
33. Maestro, version 9.0; Schrödinger, LCC: New York, NY, 2009.
34. Kaminski, G. A.; Friesner, R. A.; Tirado-Rives, J.; Jorgensen, W. L. Evaluation and reparametrization of the OPLS-AA force field for proteins via comparison with accurate quantum chemical calculations on peptides J. Phys. Chem. B 2001, 105, 6474-6487 (Pubitemid 35339015)
35. Jorgensen, W. L.; Maxwell, D. S.; TiradoRives, J. Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids J. Am. Chem. Soc. 1996, 118, 11225-11236 (Pubitemid 26399746)
36. Marelius, J.; Kolmodin, K.; Feierberg, I.; Aqvist, J. Q: a molecular dynamics program for free energy calculations and empirical valence bond simulations in biomolecular systems J. Mol. Graphics Modell. 1998, 16 (213-225) 261 (Pubitemid 30069595)
37. MacroModel, version 9.6; Schrödinger: New York, NY, 2008.
38. Jorgensen, W. L.; Chandrasekhar, J.; Madura, J. D.; Impey, R. W.; Klein, M. L. Comparison of simple potential functions for simulating liquid water J. Chem. Phys. 1983, 79, 926-935
39. Lee, F. S.; Warshel, A. A local reaction field method for fast evaluation of long-range electrostatic interactions in molecular simulations J. Chem. Phys. 1992, 97, 3100-3107
40. Ryckaert, J. P.; Ciccotti, G.; Berendsen, H. J. C. Numerical-integration of Cartesian equations of motion of a system with constraintsc - molecular-dynamics of N -alkanes J. Comput. Phys. 1977, 23, 327-341
41. Humphrey, W.; Dalke, A.; Schulten, K. VMD: Visual molecular dynamics J. Mol. Graphics 1996, 14, 33-38 (Pubitemid 26152973)
42. Desmond Molecular Dynamics System, version 2.2; D.E. Shaw Research: New York, NY, 2009.
43. Maestro-Desmond Interoperability Tools, version 2.2; Schrödinger: New York, NY, 2009.
44. Bowers, K. J.; Chow, E.; Xu, H.; Dror, R. O.; Eastwood, M. P.; Gregersen, B. A.; Klepeis, J. L.; Kolossvary, I.; Moraes, M. A.; Sacerdoti, F. D.; Salmon, J. K.; Shan, Y.; Shaw, D. E. Scalable Algrotihms for Molecular Dynamics Simulations on Commodity Clusters. Proceedings of the ACM/IEEE Conference on Supercomputing (SC06), Tampa, FL, 2006; ACM: New York, NY, 2006.
45. Pag, U.; Oedenkoven, M.; Papo, N.; Oren, Z.; Shai, Y.; Sahl, H. In vitro activity and mode of action of diastereomeric antimicrobial peptides against bacterial clinical isolates J. Antimicrob. Chemother. 2004, 53, 230-239 (Pubitemid 38239955)
46. Shai, Y.; Oren, Z. From "carpet" mechanism to de-novo designed diastereomeric cell-selective antimicrobial peptides Peptides 2001, 22, 1629-1641 (Pubitemid 32918242)
47. Oren, Z.; Hong, J.; Shai, Y. A repertoire of novel antibacterial diastereomeric peptides with selective cytolytic activity J. Biol. Chem. 1997, 272, 14643-14649 (Pubitemid 27251727)
48. Minoux, H.; Chipot, C. Cation-pi interactions in proteins: Can simple models provide an accurate description? J. Am. Chem. Soc. 1999, 121, 10366-10372 (Pubitemid 129541209)
49. Gallivan, J. P.; Dougherty, D. A. Cation-pi interactions in structural biology Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 9459-9464
50. Aliste, M. P.; MacCallum, J. L.; Tieleman, D. P. Molecular dynamics simulations of pentapeptides at interfaces: salt bridge and cation-pi interactions Biochemistry 2003, 42, 8976-8987 (Pubitemid 36935405)