Killer peptide: a novel paradigm of antimicrobial, antiviral and immunomodulatory auto-delivering drugs

Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

Bibliography

• 1  Culotta E. Funding crunch hobbles antibiotic resistance research. Science264,362–363 (1994).
  Medline CASGoogle Scholar
• 2  Bax RP. Antibiotic resistance: a view from the pharmaceutical industry. Clin. Infect. Dis.24(Suppl. 1),S5151–S5153 (1997).
  Google Scholar
• 3  Cohen ML. Changing patterns of infectious disease. Nature406,762–767 (2000).
  Medline CASGoogle Scholar
• 4  Zanetti AR, Zappa A. Emerging and re-emerging infections at the turn of the millennium. Haemophilia16(Suppl. 1),7–12 (2010).
  MedlineGoogle Scholar
• 5  Wolfe ND, Dunavan CP, Diamond J. Origins of major human infectious diseases. Nature447,279–283 (2007).
  Medline CASGoogle Scholar
• 6  Jones KE, Patel NG, Levy MA et al. Global trends in emerging infectious diseases. Nature451,990–993 (2008).
  Medline CASGoogle Scholar
• 7  Pohanka M, Kuca K. Biological warfare agents. EXS100,559–578 (2010).
  Medline CASGoogle Scholar
• 8  Woolhouse M, Gaunt E. Ecological origins of novel human pathogens. Crit. Rev. Microbiol.33,231–242 (2007).
  MedlineGoogle Scholar
• 9  Fauci AS. Infectious diseases: considerations for the 21st century. Clin. Infect. Dis.32,675–685 (2001).▪▪ Important considerations on infectious diseases and their implications for the 21st Century.
  Medline CASGoogle Scholar
• 10  Spellberg B, Guidos R, Gilbert D et al. The epidemic of antibiotic-resistant infections: a call to action for the medical community from the Infectious Diseases Society of America. Clin. Infect. Dis.46,155–164, 2008.
  MedlineGoogle Scholar
• 11  Boucher HW, Talbot GH, Bradley JS et al. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin. Infect. Dis.48,1–12 (2009).
  MedlineGoogle Scholar
• 12  Rice LB. The clinical consequences of antimicrobial resistance. Curr. Opin. Microbiol.12,476–481 (2009).▪ Recent overview of the clinical impact of antibacterial resistance.
  Medline CASGoogle Scholar
• 13  Kumar D. Emerging viruses in transplantation. Curr. Opin. Infect. Dis.23,374–378 (2010).
  MedlineGoogle Scholar
• 14  Pfaller MA, Diekema DJ. Epidemiology of invasive mycoses in North America. Crit. Rev. Microbiol.36,1–53 (2010).
  MedlineGoogle Scholar
• 15  Broder S. The development of antiretroviral therapy and its impact on the global HIV-1/AIDS pandemic. Antiviral Res.85,1–18 (2010).
  Medline CASGoogle Scholar
• 16  Nathan C. Antibiotics at the crossroads. Nature431,899–902 (2004).▪▪ Considerations on the decline of antibiotic research and development: proposals for a constructive approach to infectious disease.
  Medline CASGoogle Scholar
• 17  Czerepak EA, Ryser S. Drug approvals and failures: implications for alliances. Nature Rev. Drug Discov.7,197–198 (2008).
  CASGoogle Scholar
• 18  Projan SJ. Why is big pharma getting out of antibacterial drug discovery? Curr. Opin. Microbiol.6,427–430 (2003).
  MedlineGoogle Scholar
• 19  Service RF. Surviving the blockbuster sindrome. Science303,1796–1799 (2004).
  MedlineGoogle Scholar
• 20  Loferer H. Mining bacterial genomes for antimicrobial targets. Mol. Med. Today12,470–474 (2000).
  Google Scholar
• 21  Fischbach MA, Walsh CT. Antibiotics for emerging pathogens. Science325,1089–1093 (2009).▪▪ Recent considerations on antibiotics for emerging pathogens with emphasis on the discovery of new scaffolds using different research strategies.
  Medline CASGoogle Scholar
• 22  Rahman H, Austin B, Mitchell WJ et al. Novel anti-infective compounds from marine bacteria. Mar. Drugs8,498–518 (2010).
  Medline CASGoogle Scholar
• 23  Payne DJ, Gwynn MN, Holmes DJ, Pompliano DL. Drugs for bad bugs: confronting the challenges of antibacterial discovery. Nat. Rev. Drug Discov.6,29–40 (2007).
  Medline CASGoogle Scholar
• 24  Gross H. Genomic mining – a concept for the discovery of new bioactive natural products. Curr. Opin. Drug Discov. Devel.12,207–219 (2009).▪▪ An excellent, expert and recent review on genomic mining for the discovery of new bioactive natural products.
  Medline CASGoogle Scholar
• 25  Hammami R, Fliss I. Current trends in antimicrobial agent research: chemo- and bioinformatics approaches. Drug Discov. Today15,540–546 (2010).▪ Recent review on the progress in the development of computational methods, tools and databases used for extracting biological meaning from antimicrobial research.
  Medline CASGoogle Scholar
• 26  Fleming A. On a remarkable bacteriolytic element found in tissues and secretions. Proc. R. Soc. Lond. (Biol.)93,306–317 (1922).
  CASGoogle Scholar
• 27  Skarks RC, Watson DW. Antimicrobial factors of normal tissues and fluids. Bacteriol. Rev.21,273–294 (1957).
  MedlineGoogle Scholar
• 28  Zeya HI, Spitznagel JK. Antibacterial and enzymic basic proteins from leukocyte lysosomes: separation and identification. Science142,1085–1087 (1963).
  Medline CASGoogle Scholar
• 29  Hultmark D, Steiner H, Rasmuson T, Boman HG. Insect immunity. Purification and properties of three inducible bactericidal proteins from hemolymph of immunized pupae of Hyalophora cecropia. Eur. J. Biochem.106,7–16 (1980).
  Medline CASGoogle Scholar
• 30  Selsted ME, Brown DM, DeLange RJ, Lehrer RI. Primary structures of MCP-1 and MCP-2, natural peptide antibiotics of rabbit lung macrophages. J. Biol. Chem.258,14485–14489 (1983).
  Medline CASGoogle Scholar
• 31  Zasloff M. Antimicrobial peptides of multicellular organisms. Nature415,389–395 (2002).▪▪ Important review on the role of antimicrobial peptides of multicellular organisms in health and disease, and their potential applications.
  Medline CASGoogle Scholar
• 32  Brown KL, Hancock RE. Cationic host defense (antimicrobial) peptides. Curr. Opin. Immunol.18,24–30 (2006).
  Medline CASGoogle Scholar
• 33  Steistraesser L, Kraneburg UM, Hirsch T et al. Host defense peptides as effector molecules of the innate immune response: a sledgehammer for drug resistance? Int. J. Mol. Sci.10,3951–3970 (2009).
  MedlineGoogle Scholar
• 34  Hoskin DW, Ramamoorthy A. Studies on anticancer activities of antimicrobial peptides. Biochim. Biophys. Acta1778,357–375 (2008).
  Medline CASGoogle Scholar
• 35  Bucki R, Levental I, Janmey PA. Antibacterial peptides – a bright future or a false hope. Anti-Infect. Agents Med. Chem.6,175–184 (2007).
  CASGoogle Scholar
• 36  Boman HG. Antibacterial peptides: basic facts and emerging concepts. J. Intern. Med.254,197–215 (2003).
  Medline CASGoogle Scholar
• 37  Brogden KA. Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nat. Rev. Microbiol.3,238–250 (2005).
  Medline CASGoogle Scholar
• 38  Sahl HG, Pag U, Bonness S, Wagner S, Antcheva N, Tossi A. Mammalian defensins: structures and mechanism of antibiotic activity. J. Leukoc. Biol.77,466–475 (2005).
  Medline CASGoogle Scholar
• 39  Hale JD, Hancock REW. Alternative mechanisms of action of cationic antimicrobial peptides on bacteria. Expert Rev. Anti Infect. Ther.5,951–959 (2007).
  Medline CASGoogle Scholar
• 40  Hilpert K, McLeod B, Yu J et al. Short cationic antimicrobial peptides interact with ATP. Antimicrob. Agents Chemother.54,4480–4483 (2010).
  Medline CASGoogle Scholar
• 41  Dorschner RA, Lopez-Garcia B, Peschel A et al. The mammalian ionic environment dictates microbial susceptibility to antimicrobial defense peptides. FASEB J.20,35–42 (2006).
  Medline CASGoogle Scholar
• 42  Yeaman MR, Yount NY. Mechanisms of antimicrobial peptide action and resistance. Pharmacol. Rev.55,27–55 (2003).▪ Review of contemporary structural and functional themes among mechanisms of antimicrobial peptide action and resistance.
  Medline CASGoogle Scholar
• 43  Xu F, Meng K, Wang Y-R et al. Eukaryotic expression and antimicrobial spectrum determination of the peptide tachyplesin II. Prot. Express. Purific.58,175–183 (2008).
  Medline CASGoogle Scholar
• 44  Aerts AM, Francois IE, Cammue BP, Thevissen K. The mode of antifungal action of plant, insect and human defensins. Cell. Mol. Life Sci.65,2069–2079 (2008).▪ Review of the current knowledge concerning the mode of antifungal action of plant, insect and human defensins.
  Medline CASGoogle Scholar
• 45  Thevissen K, Warnecke DC, Francois IE et al. Defensins from insects and plants interact with fungal glucosylceramides. J. Biol. Chem.279,3900–3905 (2004).
  Medline CASGoogle Scholar
• 46  Lobo DS, Pereira IB, Fragel-Madeira L et al. Antifungal Pisum sativum defensin 1 interacts with Neurospora crassa cyclin F related to the cell cycle. Biochemistry46,987–996 (2007).
  Medline CASGoogle Scholar
• 47  Tavares PM, Thevissen K, Cammue BP et al.In vitro activity of the antifungal plant defensin RsAFP2 against Candida isolates and its in vivo efficacy in prophylactic murine models of candidiasis. Antimicrob. Agents Chemother.52,4522–4525 (2008).
  Medline CASGoogle Scholar
• 48  Klotman ME, Chang TL. Defensins in innate antiviral immunity. Nat. Rev. Immunol.6,447–456 (2006).▪ Review focusing on the antiviral activities and mechanisms of action of mammalian defensins, and on the clinical relevance of these activities.
  Medline CASGoogle Scholar
• 49  Wang W, Owen SM, Rudolph DL et al. Activity of alpha- and theta-defensins against primary isolates of HIV-1. J. Immunol.173,515–520 (2004).
  Medline CASGoogle Scholar
• 50  Yasin B, Wang W, Pang M et al. Theta defensins protect cells from infection by herpes simplex virus by inhibiting viral adhesion and entry. J. Virol.78,5147–5156 (2004).
  Medline CASGoogle Scholar
• 51  Hazrati E, Galen B, Lu W et al. Human alpha- and beta-defensins block multiple steps in herpes simplex virus infection. J. Immunol.177,8658–8666 (2006).
  Medline CASGoogle Scholar
• 52  Bastian A, Schafer H. Human alpha-defensin 1 (HNP-1) inhibits adenoviral infection in vitro. Regul. Pept.101,157–161 (2001).
  Medline CASGoogle Scholar
• 53  Buck CB, Day PM, Thompson CD et al. Human alpha-defensins block papillomavirus infection. Proc. Natl Acad. Sci. USA103,1516–1521 (2006).
  Medline CASGoogle Scholar
• 54  Dugan AS, Maginnis MS, Jordan JA et al. Human alpha-defensins inhibit BK virus infection by aggregating virions and blocking binding to host cells. J. Biol. Chem.283,31125–31132 (2008).
  Medline CASGoogle Scholar
• 55  Smith JG, Silvestry M, Lindert S, Lu W, Nemerow GR, Stewart PL. Insight into the mechanisms of adenovirus capsid disassembly from studies of defensin neutralization. PLoS Pathog.6(6),e1000959 (2010).
  MedlineGoogle Scholar
• 56  Wang G, Watson KM, Peterkofsky A, Buckheit RW Jr. Identification of novel human immunodeficiency virus type 1-inhibitory peptides based on the antimicrobial peptide database. Antimicrob. Agents Chemother.54,1343–1346 (2010).
  Medline CASGoogle Scholar
• 57  Hirsch JG. Bactericidal action of histone. J. Exp. Med.108,925–944 (1958).
  Medline CASGoogle Scholar
• 58  Frohm M, Gunne H, Bergman A-C et al. Biochemical and antibacterial analysis of human wound and blister fluid. Eur. J. Biochem.237,86–92 (1996).
  Medline CASGoogle Scholar
• 59  Shiflett AM, Bishop JR, Pahwa A, Hajduk SL. Human high-density lipoproteins are platforms for the assembly of multi-component innate immune complexes. J. Biol. Chem.280,32578–32585 (2005).
  Medline CASGoogle Scholar
• 60  Kelly BA, Harrison I, McKnight A, Dobson CB. Anti-infective activity of apolipoprotein domain derived peptides in vitro: identification of novel antimicrobial peptides related to apolipoprotein B with anti-HIV activity. BMC Immunol.11: 13 (2010).▪ Recent example of the in vitro anti-infective activity of protein-derived peptides.
  MedlineGoogle Scholar
• 61  Yang D, Chen Q, Hoover DM et al. Many chemokines including CCL20/MIP-3α display antimicrobial activity. J. Leukoc. Biol.74,448–455 (2003).
  Medline CASGoogle Scholar
• 62  Flad HD, Brandt E. Platelet-derived chemokines: pathophysiology and therapeutic aspects. Cell. Mol. Life Sci.67,2363–2386 (2010).
  Medline CASGoogle Scholar
• 63  Gonzalez-Rey E, Ganea D, Delgado M. Neuropeptides: keeping the balance between pathogen immunity and immune tolerance. Curr. Opin. Pharmacol.10,473–481 (2010).
  Medline CASGoogle Scholar
• 64  Nordahl EA, Rydengård V, Nyberg P et al. Activation of the complement system generates antibacterial peptides. Proc. Natl Acad. Sci. USA101,16879–16884 (2004).
  Medline CASGoogle Scholar
• 65  Malmsten M, Davoudi M, Walse B et al. Antimicrobial peptides derived from growth factors. Growth Factors25,60–70 (2007).
  Medline CASGoogle Scholar
• 66  Nordahl EA, Rydengård V, Mörgelin M, Schmidtchen A. Domain 5 of high molecular weight kininogen is antibacterial. J. Biol. Chem.280,34832–34839 (2005).
  Medline CASGoogle Scholar
• 67  Liepke C, Baxmann S, Heine C, Breithaupt N, Ständker L, Forssmann WG. Human hemoglobin-derived peptides exhibit antimicrobial activity: a class of host defense peptides. J. Chromatogr. B. Analyt. Technol. Biomed. Life Sci.791,345–356 (2003).
  Medline CASGoogle Scholar
• 68  Ständker L, Zachgo V, Hillemanns P, Rösinger M, Forssmann WG, Hass R. Quantitative enzyme-linked immunosorbent assay determination of an abundant hemoglobin-derived anti-infective peptide in human placenta. Anal. Biochem.401,53–60 (2010).
  MedlineGoogle Scholar
• 69  Papareddy P, Rydengård V, Pasupuleti M et al. Proteolysis of human thrombin generates novel host defense peptides. PLoS Pathog.6,e1000857 (2010).
  MedlineGoogle Scholar
• 70  Matthews T, Salgo M, Greenberg M, Chung J, DeMasi R, Bolognesi D. Enfuvirtide: the first therapy to inhibit the entry of HIV-1 into host CD4 lymphocytes. Nat. Rev. Drug Discov.3,215–225 (2004).▪▪ Comprehensive review describing discovery and development of enfuvirtide, the first peptide drug of a new class of anti-HIV agents.
  Medline CASGoogle Scholar
• 71  Lu J, Deeks SG, Hoh R et al. Rapid emergence of enfuvirtide resistance in HIV- 1-infected patients: results of a clonal analysis. J. Acquir. Immune Defic. Syndr.43,60–64 (2006).
  Medline CASGoogle Scholar
• 72  Lambert DM, Barney S, Lambert AL et al. Peptides from conserved regions of paramyxovirus fusion (F) proteins are potent inhibitors of viral fusion. Proc. Natl Acad. Sci. USA93,2186–2191 (1996).
  Medline CASGoogle Scholar
• 73  Weissenhorn W, Carfí A, Lee KH, Skehel JJ, Wiley DC. Crystal structure of the Ebola virus membrane fusion subunit, GP2, from the envelope glycoprotein ectodomain. Mol. Cell.2,605–616 (1998).
  Medline CASGoogle Scholar
• 74  Xu Y, Gao S, Cole DK et al. Basis for fusion inhibition by peptides: analysis of the heptad repeat regions of the fusion proteins from Nipah and Hendra viruses, newly emergent zoonotic paramyxoviruses. Biochem. Biophys. Res. Commun.315,664–670 (2004).
  Medline CASGoogle Scholar
• 75  Liu S, Xiao G, Chen Y et al. Interaction between the heptad repeat 1 and 2 regions in spike protein of SARS-associated coronavirus: implication for virus fusogenic mechanism and identification of fusion inhibitors. Lancet363,938–947 (2004).
  Medline CASGoogle Scholar
• 76  Territo MC, Ganz T, Selsted ME, Lehrer R. Monocyte-chemotactic activity of defensins from human neutrophils. J. Clin. Invest.84,2017–2020 (1989).
  Medline CASGoogle Scholar
• 77  Oppenheim JJ, Yang D. Alarmins: chemotactic activators of immune responses. Curr. Opin. Immunol.17,359–365 (2005).
  Medline CASGoogle Scholar
• 78  Bowdish DM, Davidson DJ, Lau YE, Lee K, Scott MG, Hancock RE. Impact of LL-37 on anti-infective immunity. J. Leukoc. Biol.77,451–459 (2005).
  Medline CASGoogle Scholar
• 79  Steinstraesser L, Kraneburg U, Jacobsen F, Al-Benna S. Host defense peptides and their antimicrobial-immunomodulatory duality. Immunobiology216,322–333 (2011).
  Medline CASGoogle Scholar
• 80  Rehaume LM, Hancock REW. Neutrophil-derived defensins as modulators of innate immune function. Crit. Rev. Immunol.28,185–200 (2008).
  Medline CASGoogle Scholar
• 81  Diamond G, Beckloff N, Weinberg A, Kisich KO. The roles of antimicrobial peptides in innate host defense. Curr. Pharm. Des.15,2377–2392 (2009).
  Medline CASGoogle Scholar
• 82  Biragyn A, Surenhu M, Yang D et al. Mediators of innate immunity that target immature, but not mature, dendritic cells induce antitumor immunity when genetically fused with non immunogenic tumor antigens. J. Immunol.167,6644–6653 (2001).
  Medline CASGoogle Scholar
• 83  Yang D, Chertov O, Oppenheim JJ. The role of mammalian antimicrobial peptides and proteins in awakening of innate host defenses and adaptive immunity. Cell. Mol. Life Sci.58,978–989 (2001).
  Medline CASGoogle Scholar
• 84  Davidson DJ, Currie AJ, Reid GS et al. The cationic antimicrobial peptide LL-37 modulates dendritic cell differentiation and dendritic cell-induced T cell polarization. J. Immunol.172,1146–1156 (2004).
  Medline CASGoogle Scholar
• 85  Tani K, Murphy WJ, Chertov O et al. Defensins act as potent adjuvants that promote cellular and humoral immune responses in mice to a lymphoma idiotype and carrier antigens. Int. Immunol.12,691–700 (2000).
  Medline CASGoogle Scholar
• 86  Scott MG, Dullaghan E, Mookherjee N et al. An anti-infective peptide that selectively modulates the innate immune response. Nat. Biotechnol.25,465–472 (2007).
  Medline CASGoogle Scholar
• 87  Mookherjee N, Hancock RE. Cationic host defence peptides: innate immune regulatory peptides as a novel approach for treating infections. Cell. Mol. Life Sci.64,922–933 (2007).
  Medline CASGoogle Scholar
• 88  Magliani W, Conti S, Cunha RL, Travassos LR, Polonelli L. Antibodies as crypts of antiinfective and antitumor peptides. Curr. Med. Chem.16,2305–2323 (2009).▪▪ Recent review describing antibodies as source of potential anti-infective and anti-tumor therapeutic peptides.
  Medline CASGoogle Scholar
• 89  Dimitrov DS, Marks JD. Therapeutic antibodies: current state and future trends - is a paradigm change coming soon? Methods Mol. Biol.525,1–27 (2009).
  Medline CASGoogle Scholar
• 90  Nelson AL, Dhimolea E, Reichert JM. Development trends for human monoclonal antibody therapeutics. Nat. Rev. Drug Discov.9,767–774 (2010).
  Medline CASGoogle Scholar
• 91  Beck A, Wurch T, Bailly C, Corvaia N. Strategies and challenges for the next generation of therapeutic antibodies. Nat. Rev. Immunol.10,345–352 (2010).
  Medline CASGoogle Scholar
• 92  Nevinsky GA, Buneva VN. Natural catalytic antibodies in norm, autoimmune, viral, and bacterial diseases. ScientificWorldJournal10,1203–1233 (2010).
  Medline CASGoogle Scholar
• 93  Magliani W, Conti S, Frazzi R, Ravanetti L, Maffei DL, Polonelli L. Protective antifungal yeast killer toxin-like antibodies. Curr. Mol. Med.5,443–452 (2005).
  Medline CASGoogle Scholar
• 94  Brena S, Omaetxebarría MJ, Elguezabal N, Cabezas J, Moragues MD, Pontón J. Fungicidal monoclonal antibody C7 binds to Candida albicans Als3. Infect. Immun.75,3680–3682 (2007).
  Medline CASGoogle Scholar
• 95  Birtalan S, Zhang Y, Fellouse FA, Shao L, Schaefer G, Sidhu SS. The intrinsic contributions of tyrosine, serine, glycine and arginine to the affinity and specificity of antibodies. J. Mol. Biol.377,1518–1528 (2008).
  Medline CASGoogle Scholar
• 96  Holliger P, Hudson PJ. Engineered antibody fragments and the rise of single domains. Nat. Biotechnol.23,1126–1136 (2005).
  Medline CASGoogle Scholar
• 97  Saerens D, Ghassabeh GH, Muyldermans S. Single-domain antibodies as building blocks for novel therapeutics. Curr. Opin. Pharmacol.8,600–608 (2008).
  Medline CASGoogle Scholar
• 98  Chen W, Zhu Z, Feng Y, Dimitrov DS. Human domain antibodies to conserved sterically restricted regions on gp120 as exceptionally potent cross-reactive HIV-1 neutralizers. Proc. Natl Acad. Sci. USA105,17121–17126 (2008).
  Medline CASGoogle Scholar
• 99  Wesolowski J, Alzogaray V, Reyelt J et al. Single domain antibodies: promising experimental and therapeutic tools in infection and immunity. Med. Microbiol. Immunol.198,157–174 (2009).
  Medline CASGoogle Scholar
• 100  Chen W, Zhu Z, Feng Y, Dimitrov DS. A large human domain antibody library combining heavy and light chain CDR3 diversity. Mol. Immunol.47,912–921 (2010).
  Medline CASGoogle Scholar
• 101  Qiu XQ, Wang H, Cai B, Wang LL, Yue ST. Small antibody mimetics comprising two complementarity-determining regions and a framework region for tumor targeting. Nat. Biotechnol.25,921–929 (2007).
  Medline CASGoogle Scholar
• 102  Ladner RC. Antibodies cut down to size. Nat. Biotechnol.25,875–877 (2007).
  Medline CASGoogle Scholar
• 103  Kang CY, Brunck TK, Kieber-Emmons T, Blalock JE, Kohler H. Inhibition of self-binding antibodies (autobodies) by a VH-derived peptide. Science240,1034–1036 (1988).
  Medline CASGoogle Scholar
• 104  Bourgeois C, Bour JB, Aho LS, Pothier P. Prophylactic administration of a complementarity-determining region derived from a neutralizing monoclonal antibody is effective against respiratory syncytial virus infection in BALB/c mice. J. Virol.72,807–810 (1998).
  Medline CASGoogle Scholar
• 105  Dorfman T, Moore MJ, Guth AC, Choe H, Farzan M. A tyrosine-sulfated peptide derived from the heavy-chain CDR3 region of an HIV-1-neutralizing antibody binds gp120 and inhibits HIV-1 infection. J. Biol. Chem.281,28529–28535 (2006).
  Medline CASGoogle Scholar
• 106  Heap CJ, Wang Y, Pinheiro TJ, Reading SA, Jennings KR, Dimmock NJ. Analysis of a 17-amino acid residue, virus-neutralizing microantibody. J. Gen. Virol.86,1791–1800 (2005).
  Medline CASGoogle Scholar
• 107  Deroo S, Fischer A, Beaupain N et al. Non-immunized natural human heavy chain CDR3 repertoires allow the isolation of high affinity peptides mimicking a human influenza hemagglutinin epitope. Mol. Immunol.45,1366–1373 (2008).
  Medline CASGoogle Scholar
• 108  Polonelli L, Magliani W, Conti S et al. Therapeutic activity of an engineered synthetic killer antiidiotypic antibody fragment against experimental mucosal and systemic candidiasis. Infect. Immun.71,6205–6212 (2003).▪▪ First report on the therapeutic activity of the killer peptide, an antibody-derived multifunctional decapeptide.
  Medline CASGoogle Scholar
• 109  Polonelli L, Pontón J, Elguezbal N et al. Antibody complementarity-determining regions (CDRs) can display differential antimicrobial, antiviral and antitumor activities. PLoS One3,e2371 (2008).▪ Demonstrates for the first time that Ab-derived complementarity-determining regions (CDRs) can display differential anti-infective and anti-tumor activities.
  MedlineGoogle Scholar
• 110  Gabrielli E, Pericolini E, Cenci E et al. Antibody complementarity-determining regions (CDRs): a bridge between adaptive and innate immunity. PLoS One4,e8187 (2009).▪ Demonstrates that isolated CDR sequences can display potent immunomodulatory activity and therapeutic effect without possessing direct antimicrobial properties. It suggests CDRs as a bridge between adaptive and innate immunity.
  MedlineGoogle Scholar
• 111  Dobroff AS, Rodrigues EG, Juliano MA et al. Differential antitumor effects of IgG and IgM monoclonal antibodies and their synthetic complementarity-determining regions directed to new targets of B16F10-Nex2 melanoma cells. Transl. Oncol.3,204–217 (2010).
  MedlineGoogle Scholar
• 112  Schmidtchen A, Pasupuleti M, Mörgelin M et al. Boosting antimicrobial peptides by hydrophobic oligopeptide end tags. Biol. Chem.284,17584–17594 (2009).
  CASGoogle Scholar
• 113  Zhang L, Falla TJ. Host defense peptides for use as potential therapeutics. Curr. Opin. Investig. Drugs10,164–171 (2009).
  Medline CASGoogle Scholar
• 114  Jenssen H, Hancock RE. Therapeutic potential of HDPs as immunomodulatory agents. Methods Mol. Biol.618,329–347 (2010).
  Medline CASGoogle Scholar
• 115  Matejuk A, Leng Q, Begum MD et al. Peptide-based antifungal therapies against emerging infections. Drugs Future35,197 (2010).
  Medline CASGoogle Scholar
• 116  Yount NY, Bayer AS, Xiong YQ, Yeaman MR. Advances in antimicrobial peptide immunobiology. Biopolymers84,435–458, (2006).
  Medline CASGoogle Scholar
• 117  Peschel A. How do bacteria resist human antimicrobial peptides? Trends Microbiol.10,179–186 (2002).
  Medline CASGoogle Scholar
• 118  Steinstraesser L, Kraneburg UM, Hirsch T et al. Host defense peptides as effector molecules of the innate immune response: a sledgehammer for drug resistance? Int. J. Mol. Sci.10,3951–3970 (2009).
  Medline CASGoogle Scholar
• 119  Bommarius B, Jenssen H, Elliott M et al. Cost-effective expression and purification of antimicrobial and host defense peptides in Escherichia coli. Peptides31,1957–1965 (2010).
  Medline CASGoogle Scholar
• 120  Giuliani A, Pirri G, Bozzi A, Di Giulio A, Aschi M, Rinaldi AC. Antimicrobial peptides: natural templates for synthetic membrane-active compounds. Cell. Mol. Life Sci.65,2450–2460 (2008).
  Medline CASGoogle Scholar
• 121  Scott RW, DeGrado WF, Tew GN. De novo designed synthetic mimics of antimicrobial peptides. Curr. Opin. Biotechnol.19,620–627 (2008).
  Medline CASGoogle Scholar
• 122  Rotem S, Mor A. Antimicrobial peptide mimics for improved therapeutic properties. Biochim. Biophys. Acta1788,1582–1592 (2009).
  Medline CASGoogle Scholar
• 123  Wang G, Li X, Wang Z. APD2: the updated antimicrobial peptide database and its application in peptide design. Nucleic Acids Res.37,D933–937 (2009).
  Medline CASGoogle Scholar
• 124  Duclohier H. Antimicrobial peptides and peptaibols, substitutes for conventional antibiotics. Curr. Pharm. Des.16,3212–3223 (2010).
  Medline CASGoogle Scholar
• 125  Tew GN, Scott RW, Klein ML, Degrado WF. De novo design of antimicrobial polymers, foldamers, and small molecules: from discovery to practical applications. Acc. Chem. Res.43,30–39 (2010).
  Medline CASGoogle Scholar
• 126  Langham A, Kaznessis YN. Molecular simulations of antimicrobial peptides. Methods Mol. Biol.618,267–285 (2010).
  Medline CASGoogle Scholar
• 127  Brouwer CP, Sarda-Mantel L, Meulemans A, Le Guludec D, Welling MM. The use of technetium-99m radiolabeled human antimicrobial peptides for infection specific imaging. Mini Rev. Med. Chem.8,1039–1052 (2008).
  Medline CASGoogle Scholar
• 128  Jenssen H, Hamill P, Hancock RE. Peptide antimicrobial agents. Clin. Microbiol. Rev.19,491–511 (2006).
  Medline CASGoogle Scholar
• 129  Marcos JF, Muñoz A, Pérez-Payá E, Misra S, López-García B. Identification and rational design of novel antimicrobial peptides for plant protection. Annu. Rev. Phytopathol.46,273–301 (2008).
  Medline CASGoogle Scholar
• 130  Zendo T, Yoneyama F, Sonomoto K. Lactococcal membrane-permeabilizing antimicrobial peptides. Appl. Microbiol. Biotechnol.88,1–9 (2010).
  Medline CASGoogle Scholar
• 131  Kindrachuk J, Napper S. Structure–activity relationships of multifunctional host defence peptides. Mini Rev. Med. Chem.10,596–614 (2010).
  Medline CASGoogle Scholar
• 132  Meng S, Xu H, Wang F. Research advances of antimicrobial peptides and applications in food industry and agriculture. Curr. Protein Pept. Sci.11,264–273 (2010).
  Medline CASGoogle Scholar
• 133  Peppas NA, Bures P, Leobandung W, Ichikawa H. Hydrogels in pharmaceutical formulations. Eur. J. Pharm. Biopharm.50,27–46 (2000).
  Medline CASGoogle Scholar
• 134  Kashyap N, Kumar N, Kumar MN. Hydrogels for pharmaceutical and biomedical applications. Crit. Rev. Ther. Drug Carrier Syst.22,107–149 (2005).
  Medline CASGoogle Scholar
• 135  Lin CC, Metters AT. Hydrogels in controlled release formulations: network design and mathematical modeling. Adv. Drug Deliv. Rev.58,1379–1408 (2006).
  Medline CASGoogle Scholar
• 136  Schmaljohann D. Thermo- and pH-responsive polymers in drug delivery. Adv. Drug Deliv. Rev.58,1655–1670 (2006).
  Medline CASGoogle Scholar
• 137  Ruel-Gariepy E, Leroux JC. In situ-forming hydrogels - review of temperature-sensitive systems. Eur. J. Pharm. Biopharm.58,409–426 (2004).
  Medline CASGoogle Scholar
• 138  Zhang S, Holmes T, Lockshin C, Rich A. Spontaneous assembly of a self-complementary oligopeptide to form a stable macroscopic membrane. Proc. Natl Acad. Sci. USA90,3334–3338 (1993).
  Medline CASGoogle Scholar
• 139  Hauser CA, Zhang S. Designer self-assembling peptide nanofiber biological materials. Chem. Soc. Rev.39,2780–2790 (2010).
  Medline CASGoogle Scholar
• 140  Zhao X, Pan F, Xu H et al. Molecular self-assembly and applications of designer peptide amphiphiles. Chem. Soc. Rev.39,3480–3498 (2010).
  Medline CASGoogle Scholar
• 141  Maji SK, Schubert D, Rivier C, Lee S, Rivier JE, Riek R. Amyloid as a depot for the formulation of long-lasting drugs. PLoS Biol.6(2),e17 (2008).
  MedlineGoogle Scholar
• 142  Salick DA, Kretsinger JK, Pochan DJ, Schneider JP. Inherent antibacterial activity of a peptide-based beta-hairpin hydrogel. J. Am. Chem. Soc.129,14793–14799 (2007).
  Medline CASGoogle Scholar
• 143  Salick DA, Pochan DJ, Schneider JP. Design of an injectable β-hairpin peptide hydrogel that kills methicillin-resistant Staphylococcus aureus. Adv. Mater.21,4120–4123 (2009).
  CASGoogle Scholar
• 144  Bevan EA, Makower M. The physiological basis of the killer character in yeast. In: Proceedings of the 11th International Congress on Genetics1,202–203 (1963).
  Google Scholar
• 145  Magliani W, Conti S, Gerloni M, Bertolotti D, Polonelli L. Yeast killer systems. Clin. Microbiol. Rev.10,369–400 (1997).
  Medline CASGoogle Scholar
• 146  Schmitt MJ, Breinig F. Yeast viral killer toxins: lethality and self-protection. Nat. Rev. Microbiol.4,212–221 (2006).
  Medline CASGoogle Scholar
• 147  Lowes KF, Shearman CA, Payne J et al. Prevention of yeast spoilage in feed and food by the yeast mycocin HMK. Appl. Environ. Microbiol.66,1066–1076 (2000).
  Medline CASGoogle Scholar
• 148  Buzzini P, Turchetti B, Vaughan-Martini AE. The use of killer sensitivity patterns for biotyping yeast strains: the state of the art, potentialities and limitations. FEMS Yeast Res.7,749–760 (2007).
  Medline CASGoogle Scholar
• 149  Pettoello-Mantovani M, Nocerino A, Polonelli L et al. Hansenula anomala killer toxin induces secretion and severe acute injury in the rat intestine. Gastroenterology109,1900–1906 (1995).
  Medline CASGoogle Scholar
• 150  Polonelli L, Lorenzini R, De Bernardis F, Morace G. Potential therapeutic effect of yeast killer toxin. Mycopathologia96,103–107 (1986).
  Medline CASGoogle Scholar
• 151  Selvakumar D, Miyamoto M, Furuichi Y, Komiyama T. Inhibition of fungal beta-1,3-glucan synthase and cell growth by HM-1 killer toxin single-chain anti-idiotypic antibodies. Antimicrob. Agents Chemother.50,3090–3097 (2006).
  Medline CASGoogle Scholar
• 152  Magliani W, Conti S, Travassos LR, Polonelli L. From yeast killer toxins to antibiobodies and beyond. FEMS Microbiol. Lett.288,1–8 (2008).
  Medline CASGoogle Scholar
• 153  Krishnaswamy S, Kabir ME, Miyamoto M, Furuichi Y, Komiyama T. Different buffer effects in selecting HM-1 killer toxin single-chain fragment variable anti-idiotypic antibodies. J. Biochem.147,723–733 (2010).
  Medline CASGoogle Scholar
• 154  Magliani W, Conti S, Giovati L, Maffei DL, Polonelli L. Anti-beta-glucan-like immunoprotective candidacidal antiidiotypic antibodies. Front. Biosci.13,6920–6937 (2008).
  Medline CASGoogle Scholar
• 155  Polonelli L, De Bernardis F, Conti S et al. Human natural yeast killer toxin-like candidacidal antibodies. J. Immunol.156,1880–1885 (1996).
  Medline CASGoogle Scholar
• 156  Torosantucci A, Bromuro C, Chiani P et al. A novel glyco-conjugate vaccine against fungal pathogens. J. Exp. Med.202,597–606 (2005).
  Medline CASGoogle Scholar
• 157  Magliani W, Conti S, Salati A et al. Therapeutic potential of yeast killer toxin-like antibodies and mimotopes. FEMS Yeast Res.5,11–18 (2004).
  Medline CASGoogle Scholar
• 158  Conti S, Magliani W, Giovati L et al. Screening of a Saccharomyces cerevisiae nonessential gene deletion collection for altered susceptibility to a killer peptide. New Microbiol.31,143–145 (2008).
  MedlineGoogle Scholar
• 159  Manfredi M, McCullough MJ, Conti S et al.In vitro activity of a monoclonal killer antiidiotypic antibody and a synthetic killer peptide against oral isolates of Candida spp. differently susceptible to conventional antifungals. Oral Microbiol. Immunol.20,226–232 (2005).
  Medline CASGoogle Scholar
• 160  Cenci E, Bistoni F, Mencacci A et al. A synthetic peptide as a novel anticryptococcal agent. Cell. Microbiol.6,953–961 (2004).
  Medline CASGoogle Scholar
• 161  Travassos LR, Silva LS, Rodrigues EG et al. Therapeutic activity of a killer peptide against experimental paracoccidioidomycosis. J. Antimicrob. Chemother.54,956–958 (2004).
  Medline CASGoogle Scholar
• 162  Donini M, Lico C, Baschieri S et al. Production of an engineered killer peptide in Nicotiana benthamiana by using a Potato virus X expression system. Appl. Environ. Microbiol.71,6360–6367 (2005).
  Medline CASGoogle Scholar
• 163  Magliani W, Conti S, Maffei DL et al. Antiidiotype-derived killer peptides as new potential tools to combat HIV-1 and AIDS-related opportunistic pathogens. Antiinf. Agents Med. Chem.6,263–272 (2007).
  CASGoogle Scholar
• 164  Savoia D, Scutera S, Raimondo S, Conti S, Magliani W, Polonelli L. Activity of an engineered synthetic killer peptide on Leishmania major and Leishmania infantum promastigotes. Exp. Parasitol.113,186–192 (2006).
  Medline CASGoogle Scholar
• 165  Fiori PL, Mattana A, Dessì D, Conti S, Magliani W, Polonelli L. In vitro acanthamoebicidal activity of a killer monoclonal antibody and a synthetic peptide. J. Antimicrob. Chemother.57,891–898 (2006).
  Medline CASGoogle Scholar
• 166  Casoli C, Pilotti E, Perno CF et al. A killer mimotope with therapeutic activity against AIDS-related opportunistic microorganisms inhibits ex vivo HIV-1 replication. AIDS20,975–980 (2006).
  MedlineGoogle Scholar
• 167  Conti G, Magliani W, Conti S et al. Therapeutic activity of an anti-idiotypic antibody-derived killer peptide against influenza A virus experimental infection. Antimicrob. Agents Chemother.52,4331–4337 (2008).
  Medline CASGoogle Scholar
• 168  Cenci E, Pericolini E, Mencacci A et al. Modulation of phenotype and function of dendritic cells by a therapeutic synthetic killer peptide. J. Leukoc. Biol.79,40–45 (2006).
  Medline CASGoogle Scholar
• 169  Pertinhez TA, Conti S, Ferrari E, Magliani W, Spisni A, Polonelli L. Reversible self-assembly: a key feature for a new class of autodelivering therapeutic peptides. Mol. Pharm.6,1036–1039 (2009).▪▪ Describes the ability of killer peptide to spontaneously and reversibly self-assemble, thus representing a novel paradigm of targeted auto-delivering drugs.
  Medline CASGoogle Scholar
• 170  Molina J, Cordero E, Pachón J. New information about the polymyxin/colistin class of antibiotics. Expert Opin. Pharmacother.10,2811–2828 (2009).
  Medline CASGoogle Scholar
• 171  Mogi T, Kita K. Gramicidin S and polymyxins: the revival of cationic cyclic peptide antibiotics. Cell. Mol. Life Sci.66,3821–3826 (2009).
  Medline CASGoogle Scholar
• 172  Magliani W, Conti S, Salati A et al. Engineered killer mimotopes: new synthetic peptides for antimicrobial therapy. Curr. Med. Chem.11,1793–1800 (2004).
  Medline CASGoogle Scholar
• 173  Brötz-Oesterhelt H, Sass P. Postgenomic strategies in antibacterial drug discovery. Future Microbiol.5,1553–1579 (2010).
  MedlineGoogle Scholar
• 174  Boguski MS, Mandl KD, Sukhatme VP. Drug discovery. Repurposing with a difference. Science324,1394–1395 (2009).
  Medline CASGoogle Scholar
• 175  Vooturi SK, Firestine SM. Synthetic membrane-targeted antibiotics. Curr. Med. Chem.17,2292–2300 (2010).
  Medline CASGoogle Scholar
• 176  Wang G, Watson KM, Peterkofsky A, Buckheit RW Jr. Identification of novel human immunodeficiency virus type 1-inhibitory peptides based on the antimicrobial peptide database. Antimicrob. Agents Chemother.54,1343–1346 (2010).
  Medline CASGoogle Scholar
• 177  Timmerman P, Barderas R, Desmet J et al. A combinatorial approach for the design of complementarity-determining region-derived peptidomimetics with in vitro anti-tumoral activity. J. Biol. Chem.284,34126–34134 (2009).
  Medline CASGoogle Scholar
• 178  Kaparissides C, Alexandridou S, Kotti K, Chaitidou S. Recent advances in novel drug delivery systems. J. Nanotechnol. Online2,1–11 (2006).
  Google Scholar
• 201  FDA-approved antiretrovial drugs.FDA-approved antiretrovial drugs. www.hivandhepatitis.com/hiv_and_aids/hiv_treat.html (Accessed 26 November 2010)
  Google Scholar
• 202  The Antimicrobial Peptide Database. http://aps.unmc.edu/AP/main.php (Accessed 15 February 2011)
  Google Scholar