Topic 2


Development of Antimicrobial peptides (AMPs) as Therapeutics

The dramatic and ever-increasing emergence of many relevant strains of bacteria resistant to traditional antibiotics (of which no radically new structural class has been introduced into medical practice over the past 30 years) is a major issue in human health. The problem is further complicated by the fact that not only has there been an explosion of resistance to antibiotics but also a rapid increase in multi-drug resistance. We have now seen the development of so called “Superbugs” that are resistant to most or all of the available antibiotics. Vertebrates and other organisms have developed a defense system to microbial infections composed of distinct groups of broad spectrum antimicrobial peptides (AMPs).

My group has been studying amphipathic α-helical AMPs for years and has made six innovative discoveries critical to the development of AMPs as therapeutics. 1) Discovery of “specificity determinants,” that is, an amino acid substitution(s) in the non-polar face of amphipathic α-helical or cyclic β-sheet AMPs that dramatically reduces toxicity to human red blood cells; 2) The development of a novel method to measure self-association of small amphipathic molecules; 3) the discovery that increasing hydrophobicity on the non-polar face beyond an optimum can lead to inactive AMPs; 4) the novel discovery that “specificity determinants” when inserted into native broad-spectrum AMPs directed selectivity to Gram-negative pathogens; 5) Methicillin-resistant S. aureus (MRSA) strains are more susceptible to AMPs than Methicillin-sensitive S. aureus (MSSA) strains. This suggested that pathogens in developing antibiotic resistance are modifying their membrane composition/structure which makes the membrane more sensitive to AMPs; 6) advances in our understanding of mechanism of action of amphipathic α-helical AMPs and the desired properties, for a clinical therapeutic; (i) the importance of lack of secondary structure in aqueous medium but inducible α-helical structure in the presence of the hydrophobic environment of the membrane; (ii) “specificity determinants” reduce or eliminate toxicity by decreasing or eliminating transmembrane penetration into eukaryotic membranes but allowing AMP access to the interface region of prokaryotic membranes; (iii) reducing self-association in aqueous environment is an important property influencing biological activity; (iv) there is an optimum hydrophobicity window to maintain high antimicrobial activity; (v) the sole target of the AMP should be the bacterial membrane and the AMP should not be involved in any stereoselective interaction with chiral enzymes or lipids or protein receptors; (vi) peptides should be prepared in the all-D conformation to provide resistance to proteolysis.

Selected publications are listed.

Jiang, Z., L. Gera, C.T. Mant and R.S. Hodges. Design of new antimicrobial peptides (AMPs) with “specificity determinants” that encode selectivity for gram-negative pathogens and remove gram-positive and hemolytic activity from broad-spectrum AMPs. In Enabling Peptide Research from Basic Research to Drug Discovery, Proceedings of the 24th American Peptide Symposium, Orlando, FL (V. Srivastava, A. Yudin and M. Lebl, editors) pp. 245-248 (2015). Published by the American Peptide Society and Propt Scientific Publishing, 2015.

Jiang, Z., A.J. Vasil, M.L. Vasil and R.S. Hodges. “Specificity determinants” improve therapeutic indices of two antimicrobial peptides Piscidin 1 and Dermaseptin S4 against gram-negative pathogens Acinetobacter baumannii and Pseudomonas aeruginosa. Pharmaceuticals 7: 366-391 (2014); DOI 10.3390/ph7040366.

Z. Jiang, A.I. Vasil, L. Gera, M.L. Vasil and R.S. Hodges. Rational design of a-helical antimicrobial peptides to target gram-negative pathogens, Acinetobacter baumannii and Pseudomonas aeruginosa: Utilization charge, “specificity determinants”, total hydrophobicity, hydrophobe type and location as design parameters to improve the therapeutic ratio. Chem. Biol & Drug Design 77: 225-240 (2011). (Journal Cover Figure) PMC3063396 PMID21219588

Hodges, R.S., Z. Jiang, J. Whitehurst, and C.T. Mant. Devleopment of antimicrobial peptides as therapeutic agents. In, “Development of Therapeutic Agents Handbook” (Ed. by Shayne C. Gad), John Wiley and Sons Inc. pp. 285-358 (2011).​

Publications

2015-2019

  1. Jiang, Z., L. Gera, C.T. Mant and R.S. Hodges. Design of new antimicrobial peptides (AMPs) with “specificity determinants” that encode selectivity for gram-negative pathogens and remove gram-positive and hemolytic activity from broad-spectrum AMPs. In Enabling Peptide Research from Basic Research to Drug Discovery, Proceedings of the 24th American Peptide Symposium, Orlando, FL (V. Srivastava, A. Yudin and M. Lebl, editors) pp. 245-248 (2015). Published by the American Peptide Society and Propt Scientific Publishing, 2015.

2010-2014

  1. Jiang, Z., A.I. Vasil, M.L. Vasil and R.S. Hodges. “Specificity determinants” improve therapeutic indices of two antimicrobial peptides Piscidin 1 and Dermaseptin S4 against gram-negative pathogens Acinetobacter baumannii and Pseudomonas aeruginosa. Pharmaceuticals 7: 366-391 (2014); DOI 10.3390/ph7040366.
  2. Z. Jiang, A.I. Vasil, L. Gera, M.L. Vasil and R.S. Hodges. Rational design of a-helical antimicrobial peptides to target gram-negative pathogens, Acinetobacter baumannii and Pseudomonas aeruginosa: Utilization charge, “specificity determinants”, total hydrophobicity, hydrophobe type and location as design parameters to improve the therapeutic ratio. Chem. Biol & Drug Design 77: 225-240 (2011). (Journal Cover Figure)
  3. Hodges, R.S., Z. Jiang, J. Whitehurst, and C.T. Mant. Devleopment of antimicrobial peptides as therapeutic agents. In, “Development of Therapeutic Agents Handbook” First Edition, edited by Shayne C. Gad), John Wiley and Sons Inc. pp. xx-xx (in press, 2011).
  4. Hartsock, W. and R.S. Hodges. Rational design of amphipathic α-helical and cyclic β-sheet antimicrobial peptides: specificity and therapeutic potential. In, “Peptide Drug Discovery and Development. Translational Research in Academia and Industry.” First Edition Castanho, M. and Santos N. (Eds.) Wiley Publishers. pp. 91-117 (2011).
  5. Jiang, Z., A.I. Vasil, L. Gera, M.L. Vasil and R.S. Hodges. Specificity determinants dramatically reduce hemolytic activity in amphipathic α-helical antimicrobial peptides: antimicrobial activity against Gram-negative pathogens, Acinetobacter baumannii and Pseudomonas aeruginosa. Proceedings of the 2010 International Conference on Antimicrobial Research, In “Science and Technology against Microbial Pathogens. Research, Development and Evaluation” World Scientific Publishing Co., Pte. Ltd. pp. 376-380 (2011).
  6. Baumgartner, H.K., N. Beeman, R.S. Hodges and M.C. Neville. A D-peptide analog of the second extracellular loop of claudin-3 and -4 leads to mis-localized claudin and cellular apoptosis in mammary epithelial cells. Chem. Biol. & Drug Design 77: 124-136 (2011). (Journal Cover Figure)
  7. Jiang, Z., M.P. Higgins, J. Whitehurst, K.O. Kisich, M.I. Voskuil and R.S. Hodges. Anti-tuberculosis activity of a-helical antimicrobial peptides: de novo designed L- and D-enantiomers versus L- and D-LL37. Protein and Peptide Letters 18: 241-252 (2011).
  8. Gambin, Y., M. Reffay, E. Sierecki, F. Homblé, R.S. Hodges, N.S. Gov, N. Taulier and W. Urbach. Variation in the lateral mobility of transmembrane peptides with hydrophobic mismatch. J. Phys. Chem. B. 114: 3559-3566 (2010).

2005-2009

  1. Reffray, M., Gambin, Y., Benabdelhak, H., Phan, G., Taulier, N., Ducruix, A., Hodges, R.S. and Urbach, W. Tracking membrane protein association in model membranes. Public library of Science 4: 1-9 (2009) (e5035) www.plosone.org..
  2. Jelokhani-Niaraki, M., L.H. Kondejewski, L. Wheaton and R.S. Hodges. Effect of ring-size on conformation and biological activity of cyclic cationic antimicrobial peptides. Journal of Medicinal Chemistry 52: 2090-2097 (2009).
  3. Jiang, Z., B.J. Kullberg, H. vander Lee, A.I. Vasil, J.D. Hale, C.T. Mant, R.E.W. Hancock, M.L. Vasil, M.G. Netea and R.S. Hodges. Effects of hydrophobicity on the anti-fungal activity of a-helical antimicrobial peptides. Chemical Biology and Drug Design 72: 483-495 (2008).
  4. Jelokhani-Niaraki, M., R.S. Hodges, J. E. Meissner, U. E. Hassenstein and L. Wheaton. Interaction of Gramicidin S and its aromatic amino acid analogues with phospholipid membranes. Biophysical Journal 95: 3306-3321 (2008).
  5. Simon, A., B.J. Kullberg, B. Tripet, O.C. Boerman, P. Zeeuwen, J. vander Ven-Jongkrijg, P. Verweij, J. Schalkwijk, R.S. Hodges, J.W.M. vander Meer, M.G. Netea. Drosomycin-like Defensin (DLD): a human homologue of Drosophila melanogaster drosomycin with antifungal activity. Antimicrobial Agents and Chemotherapy 52: 1407-1412 (2008).
  6. Jiang, Z., A.I. Vasil, J. Hale, R.E.W. Hancock, M.L. Vasil and R.S. Hodges. Effects of net charge and the number of positively charged residues on the biological activity of amphipathic a-helical cationic antimicrobial peptides. Biopolymers (Peptide Science) 90: 369-383 (2008).
  7. Abraham, T., S. Marwaha, D.M. Kobewka, R.N. Lewis, E.J. Prenner, R.S. Hodges, and R.N. McElhaney. The relationship between the binding to and permeabilization of phospholipid bilayer membranes by GS14dK4, a designed analog of the antimicrobial peptide gramicidin S. Biochimica et Biophysica Acta – Biomembranes 1768: 2089-2098 (2007).
  8. Lewis, R.N.A.H., F. Liu, R. Krivanek, R. Rybar, T. Hianik, C.R. Flach, R. Mendelsohn, Y. Chen, C.T. Mant, R.S. Hodges and R.N. McElhaney. Studies of the Minimum Hydrophobility of a-Helical Peptides Required to Maintain a Stable Transmembrane Association with Phospholipid Bilayer Membranes. Biochemistry 46: 1042-1054 (2007).
  9. Chen, Y., M.T. Guarnieri, A.I. Vasil, M.L. Vasil, C.T. Mant and R.S. Hodges. The Role of Peptide Hydrophobicity in the Mechanism of Action of a-Helical Antimicrobial Peptides Antimicrob. Agents Chemothera. 51: 1398-1406 (2007).
  10. Gambin, Y., R. Lopez-Esparza, M. Reffay, E. Sierecki, N.S. Gov, M. Genest, R.S. Hodges, and W. Urbach. Lateral Mobility of Proteins in Liquid Membranes Revisited. PNAS 103: 2098-2102 (2006).
  11. Chen, Y., A.I. Vasil, L. Rehaume, C.T. Mant, J.L. Burns, M.L. Vasil, R.E.W. Hancock, R.S. Hodges. Comparison of biophysical and biological properties of a-helical enantiomeric antimicrobial peptides. Chemical Biology and Drug Design 67: 162-173 (2006).
  12. Abraham, T., Ruthven N. A. H. Lewis, R.S. Hodges and R.N. McElhaney, Isothermal Titration Calorimetry Studies of the Binding of the Antimicrobial Peptide Gramicidin S to Phospholipid Bilayer Membranes, Biochemistry 44: 11279-11285 (2005).
  13. Abraham, T., R.N.A.H. Lewis, R.S. Hodges and R.N. McElhaney. Isothermal titration calorimetry studies of the binding of a rationally designed analogue of the antimicrobial peptide Gramicidin S to phospholipid bilayer membrances. Biochemistry 44: 2103-2112 (2005).
  14. Chen, Y., C.T. Mant, S.W. Farmer, R.E.W. Hancock, M.L. Vasil and R.S. Hodges. Rational design of a-helical antimicrobial peptides with enhanced activities and specificity/therapeutic index. J. Biol. Chem. 280: 12316-12329 (2005).
  15. Prenner, E.J., M. Kiricsi, M. Jelokhani-Niaraki, R.N.A.H. Lewis, R.S. Hodges and R.N. McElhaney. Structure-activity relationships of diastereomeric lysine ring size analogs of the antimicrobial peptide Gramicidin S: mechanism of action and discrimination between bacterial and animal cell membranes. J. Biol. Chem. 280: 2002-2011 (2005).

2000-2004

  1. Liu, F., R.N.A.H. Lewis, R.S. Hodges and R.N. McElhaney. Effect of variations in the structure of a polyleucine-based a-helical transmembrane peptide on its interaction with phosphatidylethanolamine bilayers. Biophysical Journal 87: 2470-2482 (2004).
  2. Houliston, R.S., R.S. Hodges, F.J. Sharom and J.H. Davis. Characterization of the proto-oncogenic and mutant forms of the transmembrane region of Neu in micelles. J. Biol. Chem 279: 24073-24080 (2004). Also in Proteomics Select, Vol. 3, Issue 12 (2004)
  3. Lee, D.L., J.-P.S Powers, K. Pflegerl, M.L. Vasil, R.E.W. Hancock, and R.S. Hodges. Effects of single D-amino acid substitutions on disruption of b-sheet structure and hydro­phobicity in cyclic 14-residue antimicrobial peptide analogs related to gramicidin S. J. Peptide Research 63: 69-84 (2004).
  4. Liu, F., R.N.A.H. Lewis, R.S. Hodges and R.N. McElhaney. Effect of variations in the structure of a polyleucine-based a-helical transmembrane peptide on its interaction with phosphatidylglycerol bilayers. Biochemistry 43: 3679-3687 (2004).
  5. Houliston, R. S., R. S. Hodges, F. J. Sharom and J. H. Davis. Comparison of proto-oncogenic and mutant forms of the transmembrane region of the Neu receptor in TFE. FEBS Letters 535: 39-43 (2003).
  6. Lewis, R.N.A.H., M. Kiricsi, E.J. Prenner, R.S. Hodges and R.N. McElhaney. Fourier transform infrared spectroscopic study of the interactions of a strongly antimicrobial but weakly hemolytic analog of gramicidin S with lipid micelles and lipid bilayer membranes. Biochemistry 42: 440-449 (2003).
  7. Kondejewski, L.H. and R.S. Hodges. Design, synthesis and characterization of cyclic b-sheet peptides. In: Synthesis of Peptides and Peptidomimetics. Houben-Weyl Methods of Organic Chemistry (M. Goodman, A. Felix, L. Moroder and C. Toniolo, Eds.) Thieme Stuttgart, Vol. E22d: 114-128 (2003).
  8. Lee, D.L. and R.S. Hodges. Structure-activity relationships of de novo designed cyclic antimicrobial peptides based on gramicidin S. Peptide Science ( Biopolymers) 71: 28-48 (2003).
  9. Kiricsi, M., E.J. Prenner, M. Jelokhani-Niaraki, R.N.A.H. Lewis, R.S. Hodges and R.N. McElhaney. The effects of ring-size analogs of the antimicrobial peptide gramicidin S on phospholipid bilayer model membranes and on the growth of Acholeplasma laidlawii B. Eur. J. Biochemistry 269: 5911-5920 (2002).
  10. Liu, F., R.N.A.H. Lewis, R.S. Hodges and R.N. McElhaney. Effect of variations in the structure of a polyleucine-based a-helical transmembrane peptide on its interaction with phosphatidylcholine bilayers. Biochemistry 41: 9197-9207 (2002).
  11. Jelokhani-Niaraki, M., E.J. Prenner, C.M. Kay, R.N. McElhaney and R.S. Hodges. Conformation and interaction of the cyclic cationic antimicrobial peptides in lipid bilayers. J. Peptide Res. 60: 23-36 (2002).
  12. Gibbs, A.C., T.C. Bjorndahl, R.S. Hodges and D.S. Wishart. Probing the structural determinants of Type II¢ b-turn formation in peptides and proteins. JACS 124: 1203-1213 (2002).
  13. Kondejewski, L.H., D.L. Lee, M. Jelokhani-Niaraki, S.W. Farmer, R.E.W. Hancock and R.S. Hodges. Optimization of microbial specificity in cyclic peptides by modulation of hydrophobicity within a defined structural framework. J. Biol. Chem. 277: 67-74 (2002).
  14. Zhang, Y.P., R.N. Lewis, R.S. Hodges and R.N. McElhaney. Peptide models of the helical hydrophobic transmembrane segments of membrane proteins: Interactions of acetyl-K2-(LA)12-K2-amide with phosphatidylethanolamine bilayer membranes. Biochemistry 40: 474-482 (2001).
  15. Tsapis, N., F. Reiss-Husson, R. Ober, M. Genest, R.S. Hodges and W. Urbach. Self diffusion and spectral modifications of a membrane protein, the Rubrivivax gelatinosus LH2 complex, incorporated into a monoolein cubic phase. Biophysical Journal 81: 1613-1623 (2001).
  16. Salgado, J., S.L. Grage, L.H. Kondejewski, R.S. Hodges, R.N. McElhaney and A.S. Ulrich. Membrane-bound structure and alignment of the antimicrobial b-sheet peptide gramicidin S derived from angular and distance constraints by solid-state 19F-NMR. J. Biomol. NMR 21: 191-208 (2001).
  17. Lewis, R.N.A.H., Y.-P. Zhang, R.S. Hodges, W.K. Subczynski, A. Kusimi, C.R. Flach, R. Mendelsohn and R.N. McElhaney. A polyalanine-based peptide can not form a stabletransmembrane a-helix in fully hydrated phospholipid bilayers. Biochemistry 40: 12103-12111 (2001).
  18. Jelokhani-Niaraki, M., E.J. Prenner, L.H. Kondejewski, C.M. Kay, R.N. McElhaney, and R.S. Hodges. Conformation and other biophysical properties of cyclic antimicrobial peptides in aqueous solutions. J. Peptide Res. 58: 293-306 (2001).
  19. Prenner, E.J., R.N.A.H. Lewis, M. Jelokhani-Niaraki, R.S. Hodges, and R.N. McElhaney. Cholesterol attenuates the interaction of antimicrobial peptide gramicidin S with phospholipid bilayer membranes. BBA Biomembranes 1510: 83-92 (2001).
  20. Liu, F., R.N.A.H. Lewis, R.S. Hodges and R.N. McElhaney. A differential scanning calorimetric and 31P NMR spectroscopic study of the effect of transmembrane a-helical peptides on the lamellar-reversed hexagonal phase transition of phosphatidyl­ethanol­amine model membranes. Biochemistry 40: 760-768 (2001).
  21. Jelokhani-Niaraki, M., L.H. Kondejewski, S.W. Farmer, R.E.W. Hancock, C.M. Kay and R.S. Hodges. Diasteriomeric Analogs of Gramicidin S: Structure, Biological Activity and Interaction with Lipid Bilayers. Biochem. J. 349: 747-755 (2000).
  22. McInnes, C., L.H. Kondejewski, R.S. Hodges, B.D. Sykes. Development of the Structural Basis for Antimicrobial Activities of Peptides Based on Gramicidin S and Design of Novel Analogs Using NMR Spectroscopy. J. Biol. Chem. 275: 14287-14294 (2000).
  23. Taulier, N., C. Nicot, M. Waks, R.S. Hodges, R. Ober and W. Urbach. Unbinding-binding transition induced by molecular snaps in model membranes. Biophysical J. 78: 857-865 (2000).

1995-1999

  1. Langlais, D.B., R.S. Hodges and J.H. Davis. 13C-13C rotational resonance in a trans-membrane peptide: A comparison of the fluid and gel phases. Physical Review E 59: 5945-5957 (1999).
  2. Lewis, R.N.A.H., E.J. Prenner, L.H. Kondejewski, C.R. Flach, R. Mendelson, R.S. Hodges and R.N. McElhaney. Fourier transform infrared spectroscopic studies on the interaction of the antimicrobial peptide gramicidin S with lipid micelles and with lipid monolayer and bilayer membranes. Biochemistry 38: 15193-15203 (1999).
  3. Kondejewski, L.H., M. Jelokhani-Niaraki, S.W. Farmer, C.M. Kay, B.D. Sykes, R.E.W. Hancock and R.S. Hodges. Dissociation of antimicrobial and hemolytic activities in cyclic peptide diastereomers by systematic alterations in amphipathicity. J. Biol. Chem. 274: 13181-13192 (1999).
  4. Prenner, E.J., R.N.A.H. Lewis, L.H. Kondejewski, R.S. Hodges and R.N. McElhaney. Differential scanning calorimetric study of the effect of the antimicrobial peptide gramicidin S on the thermotropic phase behavior of phosphatidylcholine, phosphotidylethanolamine and phosphatidyl glycerol lipid bilayer membranes. Biochem. Biophys. Acta 1417: 211-223 (1999).
  5. Gibbs, A.C., L.H. Kondejewski, W. Gronwald, A.M. Nip, R.S. Hodges, B.D. Sykes and D.S. Wishart. Unusual b-sheet periodicity in small cyclic peptides. Nature Structural Biol. 5: 284-288 (1998).
  6. Subczynski, W.K., R.N.A.H. Lewis, R.N. McElhaney, R.S. Hodges, J.A. Hyde and A. Kusumi. Molecular organization and dynamics of 1-palmitoyl-2-oleoylphosphatidyl choline bilayers containing a transmembrane a-helical peptide. Biochem. 37: 3156-3164 (1998).
  7. Houston, M.E., L.H. Kondejewski, D.N. Karunaratue, M. Gough, S. Fidai, R.S. Hodges and R.E.W. Hancock. Influence of preformed a-helix and a-helix induction on the activity of cationic antimicrobial peptides. J. Peptide Research 52: 81-88 (1998).
  8. Prenner, E.J., R.N.A.H. Lewis, K.C. Neuman, S.M. Gruner, L.H. Kondejewski, R.S. Hodges and R.N. McElhaney. Nonlamellar phases induced by the interaction of Gramicidin S with lipid bilayers. A possible relationship to membrane-disrupting activity. Biochemistry 36: 7906-7916 (1997).
  9. Kondejewski, L.H., S.W. Farmer, D.S. Wishart, C.M. Kay, R.E.W. Hancock and R.S. Hodges. Modulation of structure and antibacterial and hemolytic activity by ring size in cyclic Gramicidin S analogs. J. Biol. Chem. 271: 25261-25268 (1996).
  10. Wishart, D.S., L.H. Kondejewski, P.D. Semchuk, B.D. Sykes and R.S. Hodges. A method for the facile solid-phase synthesis of gramicidin S and its analogs. Lett. Pept. Sci. 3: 53-60 (1996).
  11. Kondejewski, L.H., S.W. Farmer, D.S. Wishart, R.E.W. Hancock and R.S. Hodges. Gramicidin S is active against gram negative bacteria. Int. Journal Peptide Protein Res. 47: 460-466 (1996).
  12. Davis, J.H., M. Auger and R.S. Hodges. High Resolution 'H NMR of a trans-membrane peptide. Biophysical Journal 69: 1917-1932 (1995).
  13. Zhang, Y.P., R.N.A.H. Lewis, R.S. Hodges and R.N. McElhaney. Peptide models of helical hydrophobic transmembrane segments of membrane proteins II. Differential scanning calorimetric and FTIR spectroscopic studies of the interaction of Ac-K2(LA)12K2-amide with phosphatidylcholine bilayers. Biochemistry 34: 2362-2371 (1995).
  14. Y.P. Zhang, R.N.A.H. Lewis, G.D. Henry, B.D. Sykes, R.S. Hodges and R.N. McElhaney. Peptide models of helical hydrophobic transmembrane segments of membrane proteins. 1. Studies of the conformation, intrabilayer orientation and amide hydrogen exchangeability of Ac-K2-(LA)12-K2-Amide. Biochemistry 34: 2348-2361 (1995).
  15. Zhang, Y.-P., R.N.A.H. Lewis, R.S. Hodges and R.N. McElhaney. Interaction of a peptide model of a hydrophobic transmembrane a-helical segment of a membrane protein with phosphatidylethanolamine bilayers: Differential scanning calorimetric and FTIR spectroscopic studies. Biophysical Journal 68: 847-857 (1995).
  16. Wishart, D.S., L.H. Kondejewski, P.D. Semchuk, C.M. Kay, R.S. Hodges and B.D. Sykes. Design, synthesis and characterization of a water-soluble β-sheet peptide. In: "Techniques in Protein Chemistry VI", (J.W. Crabb, Ed.). Academic Press Inc. pp. 451-466 (1995).

1990-1994

  1. Zhang, Y.-P., R.N.A.H. Lewis, R.S. Hodges and R.N. McElhaney. Interaction of a peptide model of a hydrophobic transmembrane a-helical segment of a membrane protein with phosphatidylcholine bilayers: Differential scanning calorimetric and FTIR spectroscopic studies. Biochemistry 31: 11579-11588 (1992).
  2. Zhang, Y.-P., R.N.A.H. Lewis, R.S. Hodges and R.N. McElhaney. FTIR spectroscopic studies of the conformation and amide hydrogen exchange of a peptide model of the hydrophobic transmembrane a-helices of membrane proteins. Biochemistry 31: 11572-11578 (1992).

1985-1989

  1. Roux, M., J.-M. Neuman, R.S. Hodges, P.F. Devaux and M. Bloom. Conformational changes of phospholipid head groups induced by a cationic integral membrane peptide as seen by deuterium magnetic resonance. Biochemistry 28: 2313-2321 (1989).
  2. Pauls, K.P., A.L. MacKay, O. Soderman, M. Bloom, A.K. Taneja and R.S. Hodges. Dynamic properties of the backbone on an integral membrane polypeptide as measured by 2H-NMR. Eur. Biophys. J. 12: 1-11 (1985).
  3. Huschilt, J.C., R.S. Hodges and J.H. Davis. Phase equilibria in an amphiphilic peptide-phospholipid model membrane by 2H-nuclear magnetic resonance difference spectroscopy. Biochemistry 24:1377-1386 (1985).

1980-1984

  1. Davis, J.H., D.M. Clare, R.S. Hodges and M. Bloom. The interaction of a synthetic amphiphilic polypeptide and lipids in a bilayer structure. Biochemistry 22: 5298-5305 (1983).
  2. Davis, J.H., R.S. Hodges and M. Bloom. The interaction between a synthetic amphiphilic polypeptide and lipids. Biophys. J. 37: 170-171 (1982).​
​ ​​

Proceedings Publications

2015-2019

  1. Hodges, R.S. and Z. Jiang. Design of new antimicrobial peptides (AMPs): “Specificity Determinants” erode gram-negative pathogen selectivity and remove both gram-positive activity and hemolytic activity from broad-spectrum AMPs. First International Caparica Conference in Antibiotic Resistance, Caparica, Portugal 2015. IC2AR2015 Proceedings (C. Lodeiro, J.L. Capelo, H.M. Santos, E. Oliveira, C. Nunez-Glez, J.E. Araujo and A.F. Lodeiro, editors) p. 84 (2015) (www.IC2AR.com).

2010-2014

  1. Abraham, T., E.J. Prenner, R.N.A.H. Lewis, C.T. Mant, S. Keller, R.S. Hodges and R.N. McElhaney. Structure-activity relationships of the antimicrobial peptide gramicidin S and its analogs: Aqueous solubility, self-association, conformation, antimicrobial activity and interaction with model lipid membranes. Biochim. Biophys. Acta 1838: 1420-1429 (2014). No PMC or PMID
  2. Hackbarth, C.L. and R.S. Hodges. Antigenic determinants of cross-reactivity in the development of a Pseudomonas aeruginosa peptide vaccine targeting the receptor binding domain of the Type IV pilus. In Peptides: Building Bridges (M. Lebl, Ed.), Proceedings of the 22nd Amercan Peptide Symposium,San Diego, CA, pp. 146-147 (2011).
  3. Hartsock, W.J., Z. Jiang, L. Gera, C.T. Mant, D.I. Vasil, M. Vasil and R.S. Hodges. Evaluation an α-helical antimicrobial peptide targeting gram-negative pathogens in a systemic animal model. In Peptides: Building Bridges (M. Lebl, Ed.), Proceedings of the 22nd American Peptide Symposium, San Diego, CA, pp. 144-145 (2011).
  4. Jiang, Z., A.I. Vasil, M.L. Vasil, and R.S. Hodges. Effect of net positive charge and charge distribution on the polar face of amphipathic a-helical antimicrobial peptides on their biological and biophysical properties. In Breaking Away: Proccedings of the 21st American Peptide Symposium. Bloomington, IN, (2009), M. Lebl (Ed.), American Peptide Society 266-267 (2010).

2005-2009

  1. Jiang, Z., A.I. Vasil, J. Hale, R.E.W. Hancock, M.L. Vasil and R.S. Hodges. Effects of net charge and number of positively charged residues on the biological activity of amphipathic a-helical cationic antimicrobial peptides. In Peptides for Youth, Proceedings of the 20th American Peptide Symposium, Montreal, Quebec, Canada (2007). (S. Del Valle, E. Escher, W.D. Lubell, (Eds) Springer p. 561-562 (2009) and Adv. Exp. Med. Biol. 611: 561-562 (2009).
  2. Chen, Y., M. Guarnieri, M. Vasil and R.S. Hodges. Rational Design of a-Helical Antimicrobial Peptides. In Understanding Biology Using Peptides: Proceedings of the 19th American Peptide Symposium. San Diego, CA (2005) (S.E. Blondelle, Ed.) Springer Science, New York, NY pp 291-292 (2006).
  3. Chen, Y. and R.S. Hodges. Rational design of a-helical antimicrobial peptides with improved specificity. In “Peptides, Biology and Chemistry; Proceedings of the 2004 Chinese Peptide Symposium, Kunming, China,” Ke-Llang Liu and James Tam, Eds. Science Press USA 2005 pp. 46-48.
  4. Jelokhani-Niaraki, M., E.J. Prenner and R. S. Hodges. Biophysical Studies of Cyclic Cationic Antimicrobial Peptides. “Proceedings of the 1st Asia-Pacific International Peptide Symposium (APIPS), Fukuoka, Japan Oct 31-Nov 3, 2004” In Peptide Science 2004 (Y. Shimohigashi, Ed.) Japanese Peptide Society, pp. 75-78 (2005).

2000-2004

  1. Jelokhani-Niaraki, M., L.H. Kondejewski, C.M. Kay and R.S. Hodges. Variation in ring size of cyclic antimicrobial peptides results in diversity and selectivity of biological activity. In “Peptides: The Wave of the Future”, Proceedings of the Second International/Seventeenth American Peptide Symposium (M. Lebl and R.A. Houghten, Eds.), Kluwer Academic Publishers, pp. 497-498 (2001).
  2. Lee, D.L., S.W. Farmer, K. Pflegerl, R.E.W. Hancock, M.L. Vasil and R.S. Hodges. Disruption of the b-sheet structure of cyclic peptides by single amino acid substitution: influence on prokaryotic and eukaryotic cell viability. In “Peptides: The Wave of the Future”, Proceedings of the Second International/Seventeenth American Peptide Symposium (M. Lebl and R.A. Houghten, Eds.), Kluwer Academic Publishers, pp. 477-478 (2001).
  3. Kondejewski, L.H., C. McInnes, M. Jelokhani-Niaraki, S.W. Farmer, C.M. Kay, B.D. Sykes, R.E.W. Hancock and R.S. Hodges. Modulation of specificity in cyclic antimicrobial peptides by amphipathicity. In Peptides for the New Millennium”, Proceedings of the Sixteenth American Peptide Symposium (G.B. Fields, J.P. Tam and G. Barany, Eds.), Kluwer Academic Publishers, pp. 752-753 (2000).
  4. Jelokhani-Niaraki, M., E.J. Prenner, L.H. Kondejewski, R.N. McElhaney, C.M. Kay and R.S. Hodges. Interaction of Gramicidin S and its biologically active analogs with phospholipid bilayers. InPeptides for the New Millennium”, Proceedings of the Sixteenth American Peptide Symposium (G.B. Fields, J.P. Tam and G. Barany, Eds.), Kluwer Academic Publishers, pp. 740-741 (2000).
  5. Semchuk, P.D., M. Genest, L.H. Kondejewski and R.S. Hodges. Minimization of side reactions during removal of the formyl protecting group from the  amino group of lysine. In “Peptides for the New Millennium”, Proceedings of the Sixteenth American Peptide Symposium (G.B. Fields, J.P. Tam and G. Barany, Eds.), Kluwer Academic Publishers, pp. 120-121 (2000).

1995-1999

  1. Jelokhani-Niaraki, M., L.H. Kondejewski, Y. Chen, R.E.W. Hancock, C.M. Kay and R.S. Hodges. Structure and Biological Activity of Cyclic Peptides Based on Gramicidin S. Proceedings of the 35th Japanese Peptide Symposium. Peptide Science 1998: M. Kondo (Ed.). Protein Research Foundation, Osaka, pp. 81-84 (1999).
  2. Kondejewski, L.H., M. Jelokhani-Niaraki, E.J. Prenner, R.N.A.H. Lewis, R.N. McElhaney, R.E.W. Hancock and R.S. Hodges. Design of cyclic antimicrobial peptides with low hemolytic activity. InPeptide Science - Present and Future, Proceedings of the First International Peptide Symposium, Kluwer Academic Publishers, Y. Shimonishi, Ed., pp. 88-91 (1999).
  3. McMullen, T.P.W., E.J. Prenner, R.N.A.H. Lewis, L.H. Kondejewski, R.S. Hodges and R.N. McElhaney. The interaction between gramicidin S and lipid bilayers: Evidence for cholesterol attenuation of phospholipid-peptide interactions. In Peptides: Frontiers of Peptide Science, Proceedings of the Fifteenth American Peptide Symposium (J. Tam and P. Kaumaya, Eds.) Kluwer Academic Publishers, pp. 639-640 (1999).
  4. Kondejewski, L.H., M. Jelokhani-Niaraki, R.E.W. Hancock and R.S. Hodges. Structure-activity relationships in cyclic ß-sheet antibacterial peptides. In Peptides: Frontiers of Peptide Science, Proceedings of the Fifteenth American Peptide Symposium (J. Tam and P. Kaumaya, Eds.) Kluwer Academic Publishers, pp. 152-153 (1999).
  5. Kondejewski, L.H., D.S. Wishart, B.D. Sykes, C.M. Kay and R.S. Hodges. Design, synthesis and characterization of a peptide ß-sheet model. In: Peptides: Chemistry, Structure and Biology, Proceedings of the Fourteenth American Peptide Symposium (P. Kaumaya and R.S. Hodges, Eds.) Mayflower Scientific Ltd., England, pp. 68-70 (1996).​

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