Abstract
In recent years, the increase of invasive fungal infections and the emergence of antifungal resistance stressed the need for new antifungal drugs. Peptides have shown to be good candidates for the development of alternative antimicrobial agents through high-throughput screening, and subsequent optimization according to a rational approach. This review presents a brief overview on antifungal natural peptides of different sources (animals, plants, micro-organisms), peptide fragments derived by proteolytic cleavage of precursor physiological proteins (cryptides), synthetic unnatural peptides and peptide derivatives. Antifungal peptides are schematically reported based on their structure, antifungal spectrum and reported effects. Natural or synthetic peptides and their modified derivatives may represent the basis for new compounds active against fungal infections.
Papers of special note have been highlighted as: • of interest
References
- 1 . Hidden killers: human fungal infections. Sci. Transl. Med. 4(165), 165rv113 (2012).
- 2 . How to bolster the antifungal pipeline. Science 347(6229), 1414–1416 (2015).
- 3 . Peptide therapeutics: current status and future directions. Drug Discov. Today 20(1), 122–128 (2015).
- 4 . Synthetic therapeutic peptides: science and market. Drug Discov. Today 15(1–2), 40–56 (2010).
- 5 . Discovery and development of first in class antifungal caspofungin (CANCIDAS(R)) – a case study. Nat. Prod. Rep. 31(1), 15–34 (2014).
- 6 Executive summary: clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin. Infect. Dis. 62(4), 409–417 (2016).
- 7 . Antimicrobial peptides: promising compounds against pathogenic microorganisms. Curr. Med. Chem. 21(20), 2299–2321 (2014). • Updated and comprehensive review on antimicrobial peptides (AMPs), their current pharmacological development and potential therapeutic applications.
- 8 . Factors affecting antimicrobial activity of MUC7 12-mer, a human salivary mucin-derived peptide. Ann. Clin. Microbiol. Antimicrob. 6(1), 1–10 (2007).
- 9 . Insights into the antimicrobial properties of hepcidins: advantages and drawbacks as potential therapeutic agents. Molecules 20(4), 6319–6341 (2015).
- 10 . Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nat. Rev. Microbiol. 3(3), 238–250 (2005).
- 11 . Antimicrobial peptides from plants. Pharmaceuticals 8(4), 711–757 (2015).
- 12 . Antifungal plant defensins: mechanisms of action and production. Molecules 19(8), 12280–12303 (2014).
- 13 Structure of the lipodepsipeptide syringomycin E in phospholipids and sodium dodecylsulphate micelle studied by circular dichroism, NMR spectroscopy and molecular dynamics. BBA Biomembranes 1808(9), 2102–2110 (2011).
- 14 . Antifungal proteins: more than antimicrobials? Fungal Biol. Rev. 26(4), 132–145 (2013).
- 15 . Properties and mechanisms of action of naturally occurring antifungal peptides. Cell. Mol. Life Sci. 70(19), 3545–3570 (2013). • Extensive and in-depth review on natural occurring antifungal peptides from diverse sources, outlining their complex mechanism of action.
- 16 . Apoptosis-inducing antifungal peptides and proteins. Biochem. Soc. Trans. 39(5), 1527–1532 (2011).
- 17 . The host's reply to Candida biofilm. Pathogens 5(1), pii: E33 (2016).
- 18 . Fungal biofilm resistance. Int. J. Microbiol. 2012, 528521 (2012).
- 19 . Defensins: antifungal lessons from eukaryotes. Front. Microbiol. 5, 97 (2014).
- 20 Antifungal compounds from Cyanobacteria. Mar. Drugs 13(4), 2124 (2015).
- 21 . An overview of antifungal peptides derived from insect. Peptides 80, 80–88 (2016).
- 22 . Marine peptides and their anti-infective activities. Mar. Drugs 13(1), 618–654 (2015).
- 23 . APD3: the antimicrobial peptide database as a tool for research and education. Nucleic Acids Res. 44(D1), D1087–1093 (2016).
- 24 . BaAMPs: the database of biofilm-active antimicrobial peptides. Biofouling 31(2), 193–199 (2015).
- 25 . Commercialization of antifungal peptides. Fungal Biol. Rev. 26(4), 156–165 (2013).
- 26 Induction of yeast apoptosis by an antimicrobial peptide, Papiliocin. Biochem. Biophys. Res. Commun. 408(1), 89–93 (2011).
- 27 Antifungal effect and action mechanism of antimicrobial peptide polybia-CP. J. Pept. Sci. 22(1), 28–35 (2016).
- 28 Antimicrobial peptide protonectin disturbs the membrane integrity and induces ROS production in yeast cells. BBA Biomembranes 1848(10, Part A), 2365–2373 (2015).
- 29 . Antifungal effect and pore-forming action of lactoferricin B like peptide derived from centipede Scolopendra subspinipes mutilans. BBA Biomembranes 1828(11), 2745–2750 (2013).
- 30 . The antimicrobial peptide arenicin-1 promotes generation of reactive oxygen species and induction of apoptosis. BBA General Subjects 1810(12), 1246–1251 (2011).
- 31 Lead optimization of antifungal peptides with 3D NMR structures analysis. Protein Sci. 13(3), 703–713 (2004).
- 32 . Gambicin: a novel immune responsive antimicrobial peptide from the malaria vector Anopheles gambiae. Proc. Natl Acad. Sci. USA 98(22), 12630–12635 (2001).
- 33 Cloning and purification of the first termicin-like peptide from the cockroach Eupolyphaga sinensis. J. Venom. Anim. Toxins Incl. Trop. Dis. 22, 5 (2016).
- 34 . Theonellamide G, a potent antifungal and cytotoxic bicyclic glycopeptide from the Red Sea marine sponge Theonella swinhoei. Mar. Drugs 12(4), 1911–1923 (2014).
- 35 . Naturally occurring peptides from Rana temporaria: antimicrobial properties and more. Curr. Top. Med. Chem. 16(1), 54–64 (2016).
- 36 . An overview of Brevinin superfamily: structure, function and clinical perspectives. Adv. Exp. Med. Biol. 818, 197–212 (2014).
- 37 Peptide-based antifungal therapies against emerging infections. Drugs Future 35(3), 197 (2010).
- 38 Fungicidal activity of five cathelicidin peptides against clinically isolated yeasts. J. Antimicrob. Chemother. 58(5), 950–959 (2006).
- 39 . Antifungal activity of cathelicidin peptides against planktonic and biofilm cultures of Candida species isolated from vaginal infections. Peptides 71, 211–221 (2015).
- 40 Assessing the potential of four cathelicidins for the management of mouse candidiasis and Candida albicans biofilms. Biochimie 121, 268–277 (2016).
- 41 . Delineation of an active fragment and poly(l-proline) II conformation for candidacidal activity of Bactenecin 5. Biochemistry (Mosc.) 35(14), 4314–4325 (1996).
- 42 Structural and functional characterization of the porcine proline-rich antifungal peptide SP-B isolated from salivary gland granules. J. Pept. Sci. 14(3), 251–260 (2008).
- 43 Structural and functional studies on a proline-rich peptide isolated from swine saliva endowed with antifungal activity towards Cryptococcus neoformans. BBA Biomembranes 1828(3), 1066–1074 (2013).
- 44 . Synthesis and characterization of defensin NP-1. Int. J. Pept. Protein Res. 40(6), 507–514 (1992).
- 45 Unraveling the antifungal activity of a South American rattlesnake toxin crotamine. Biochimie 95(2), 231–240 (2013).
- 46 . How does it kill? Understanding the candidacidal mechanism of salivary Histatin 5. Eukaryot. Cell 13(8), 958–964 (2014).
- 47 . Interplay between Candida albicans and the antimicrobial peptide armory. Eukaryot. Cell 13(8), 950–957 (2014).
- 48 Antifungal activity of the noncytotoxic human peptide Hepcidin 20 against fluconazole-resistant Candida glabrata in human vaginal fluid. Antimicrob. Agents Chemother. 57(9), 4314–4321 (2013).
- 49 The radish defensins RsAFP1 and RsAFP2 act synergistically with caspofungin against Candida albicans biofilms. Peptides 75, 71–79 (2016).
- 50 . Synthesis, structural characterization, and bioactivity of the stable peptide RCB-1 from Ricinus communis. J. Nat. Prod. 78(11), 2545–2551 (2015).
- 51 The antifungal plant defensin AhPDF1.1b is a beneficial factor involved in adaptive response to zinc overload when it is expressed in yeast cells. MicrobiologyOpen 4(3), 409–422 (2015).
- 52 Synergistic activity of the plant defensin HsAFP1 and caspofungin against Candida albicans biofilms and planktonic cultures. PLoS ONE 10(8), e0132701 (2015).
- 53 . Identification and mechanism of action of the plant defensin NaD1 as a new member of the antifungal drug arsenal against Candida albicans. Antimicrob. Agents Chemother. 57(8), 3667–3675 (2013).
- 54 The role of thionins in rice defence against root pathogens. Mol. Plant Pathol. 16(8), 870–881 (2015).
- 55 . Sesquin a potent defensin-like antimicrobial peptide from ground beans with inhibitory activities toward tumor cells and HIV-1 reverse transcriptase. Peptides 26(7), 1120–1126 (2005).
- 56 Disulfide-stabilized helical hairpin structure and activity of a novel antifungal peptide EcAMP1 from seeds of barnyard grass (Echinochloa crus-galli). J. Biol. Chem. 286(28), 25145–25153 (2011).
- 57 Novel antifungal alpha-hairpinin peptide from Stellaria media seeds: structure, biosynthesis, gene structure and evolution. Plant Mol. Biol. 84(1–2), 189–202 (2014).
- 58 . Plant antimicrobial peptides snakin-1 and snakin-2: chemical synthesis and insights into the disulfide connectivity. Chemistry 20(17), 5102–5110 (2014).
- 59 . Identification of an antifungal peptide from Trapa natans fruits with inhibitory effects on Candida tropicalis biofilm formation. Peptides 32(8), 1741–1747 (2011).
- 60 Plant-derived decapeptide OSIP108 interferes with Candida albicans biofilm formation without affecting cell viability. Antimicrob. Agents Chemother. 58(5), 2647–2656 (2014).
- 61 Novel proline-hydroxyproline glycopeptides from the dandelion (Taraxacum officinale Wigg.) flowers: de novo sequencing and biological activity. Plant Sci. 238, 323–329 (2015).
- 62 Antimicrobial peptides from Amaranthus caudatus seeds with sequence homology to the cysteine/glycine-rich domain of chitin-binding proteins. Biochemistry (Mosc.) 31(17), 4308–4314 (1992).
- 63 A novel antifungal peptide from leaves of the weed Stellaria media L. Biochimie 116, 125–132 (2015).
- 64 . Discovery of six families of fungal defensin-like peptides provides insights into origin and evolution of the CSalphabeta defensins. Mol. Immunol. 45(3), 828–838 (2008).
- 65 In vivo application of a small molecular weight antifungal protein of Penicillium chrysogenum (PAF). Toxicol. Appl. Pharmacol. 269(1), 8–16 (2013).
- 66 Antifungal properties of durancins isolated from Enterococcus durans A5–11 and of its synthetic fragments. Lett. Appl. Microbiol. 56(4), 237–244 (2013).
- 67 . Antagonistic activities of novel peptides from Bacillus amyloliquefaciens PT14 against Fusarium solani and Fusarium oxysporum. J. Agric. Food Chem. 63(48), 10380–10387 (2015).
- 68 . Properties of the bubble protein, a defensin and an abundant component of a fungal exudate. Peptides 32(10), 1989–1995 (2011).
- 69 . Survival strategies of yeast and filamentous fungi against the antifungal protein AFP. J. Biol. Chem. 286(16), 13859–13868 (2011).
- 70 . Characterization and expression of the antifungal protein from Monascus pilosus and its distribution among various Monascus species. J. Biosci. Bioeng. 122(1), 27–33 (2016).
- 71 Burkholdines from Burkholderia ambifaria: antifungal agents and possible virulence factors. J. Nat. Prod. 75(9), 1518–1523 (2012).
- 72 . Bacillus lipopeptides: versatile weapons for plant disease biocontrol. Trends Microbiol. 16(3), 115–125 (2008).
- 73 Lipopeptide induces apoptosis in fungal cells by a mitochondria-dependent pathway. Peptides 31(11), 1978–1986 (2010).
- 74 Balticidins A–D, antifungal hassallidin-like lipopeptides from the Baltic Sea cyanobacterium Anabaena cylindrica Bio33. J. Nat. Prod. 77(6), 1287–1296 (2014).
- 75 Curvularides A–E: antifungal hybrid peptide-polyketides from the endophytic fungus Curvularia geniculata. Chem. Eur. J. 16(36), 11178–11185 (2010).
- 76 Isolation, structure, and biological activity of Phaeofungin, a cyclic lipodepsipeptide from a Phaeosphaeria sp. using the genome-wide Candida albicans fitness test. J. Nat. Prod. 76(3), 334–345 (2013).
- 77 . Analyzing the cryptome: uncovering secret sequences. AAPS J. 13(2), 152–158 (2011). • Concise but comprehensive review on different approaches and proteomic tools for discovering, identifying and characterizing cryptides.
- 78 Anti-candidal activity of a novel peptide derived from human chromogranin A and its mechanism of action against Candida krusei. Exp. Ther. Med. 10(5), 1768–1776 (2015).
- 79 . Abhisin: a potential antimicrobial peptide derived from histone H2A of disk abalone (Haliotis discus discus). Fish Shellfish Immunol. 27(5), 639–646 (2009).
- 80 Acipensins – novel antimicrobial peptides from leukocytes of the russian sturgeon Acipenser gueldenstaedtii. Acta Naturae 6(4), 99–109 (2014).
- 81 . Loss of mannosylphosphate from Candida albicans cell wall proteins results in enhanced resistance to the inhibitory effect of a cationic antimicrobial peptide via reduced peptide binding to the cell surface. Microbiology 155(4), 1058–1070 (2009).
- 82 A hemocyanin-derived antimicrobial peptide from the penaeid shrimp adopts an alpha-helical structure that specifically permeabilizes fungal membranes. BBA Gen. Subjects 1860(3), 557–568 (2016).
- 83 . Human hemoglobin-derived peptides exhibit antimicrobial activity: a class of host defense peptides. J. Chromatogr. B 791(1–2), 345–356 (2003).
- 84 . Recent studies on the antimicrobial peptides lactoferricin and lactoferrampin. Curr. Mol. Med. 14(9), 1139–1154 (2014).
- 85 . Antimicrobial peptide MUC7 12-mer activates the calcium/calcineurin pathway in Candida albicans. FEMS Yeast Res. 10(5), 579–586 (2010).
- 86 . MUC7 20-Mer: investigation of antimicrobial activity, secondary structure, and possible mechanism of antifungal action. Antimicrob. Agents Chemother. 47(2), 643–652 (2003).
- 87 Structure–activity relations of parasin I, a histone H2A-derived antimicrobial peptide. Peptides 29(7), 1102–1108 (2008).
- 88 Increased potency of a novel d-β-naphthylalanine-substituted antimicrobial peptide against fluconazole-resistant fungal pathogens. FEMS Yeast Res. 9(6), 967–970 (2009).
- 89 . P-113 peptide: new experimental evidences on its biological activity and conformational insights from molecular dynamics simulations. Biopolymers (Peptide Sci.) 102(2), 159–167 (2014).
- 90 Truncation of amidated fragment 33–61 of bovine alpha-hemoglobin: effects on the structure and anticandidal activity. Biopolymers 88(3), 413–426 (2007).
- 91 A peptide derived from the highly conserved protein GAPDH is involved in tissue protection by different antifungal strategies and epithelial immunomodulation. J. Invest. Dermatol. 133(1), 144–153 (2013).
- 92 Therapeutic activity of an engineered synthetic killer antiidiotypic antibody fragment against experimental mucosal and systemic candidiasis. Infect. Immun. 71(11), 6205–6212 (2003).
- 93 Peptides of the constant region of antibodies display fungicidal activity. PLoS ONE 7(3), e34105 (2012).
- 94 Inhibition of adherence and killing of Candida albicans with a 23-Mer peptide (Fn/23) with dual antifungal properties. Antimicrob. Agents Chemother. 48(11), 4337–4341 (2004).
- 95 Peptide derived from anti-idiotypic single-chain antibody is a potent antifungal agent compared with its parent fungicide HM-1 killer toxin peptide. Appl. Microbiol. Biotechnol. 92(6), 1151–1160 (2011).
- 96 Antibody complementarity-determining regions (CDRs) can display differential antimicrobial, antiviral and antitumor activities. PLoS ONE 3(6), e2371 (2008).
- 97 The neuropeptide α-MSH in host defense. Ann. NY Acad. Sci. 917(1), 227–231 (2000).
- 98 . Antimicrobial peptides: an alternative for innovative medicines? Appl. Microbiol. Biotechnol. 99(5), 2023–2040 (2015). • Recent mini-review on available strategies for AMPs synthesis and bioinformatic tools for rational design of novel therapeutic agents.
- 99 . Antimicrobial peptides and their analogs: searching for new potential therapeutics. Perspect. Medicin. Chem. 6, 73–80 (2014).
- 100 . Tryptophan-rich antimicrobial peptides: comparative properties and membrane interactions. Biochem. Cell Biol. 80(5), 667–677 (2002).
- 101 Mechanism of action of novel synthetic dodecapeptides against Candida albicans. Biochim. Biophys. Acta 1830(11), 5193–5203 (2013).
- 102 Boosting salt resistance of short antimicrobial peptides. Antimicrob. Agents Chemother. 57(8), 4050–4052 (2013).
- 103 . Endocytosis-mediated vacuolar accumulation of the human ApoE apolipoprotein-derived ApoEdpL-W antimicrobial peptide contributes to its antifungal activity in Candida albicans. Antimicrob. Agents Chemother. 55(10), 4670–4681 (2011).
- 104 . Synthesis, biological activity and conformational analysis of head-to-tail cyclic analogues of LL37 and histatin 5. J. Pept. Sci. 18(9), 560–566 (2012).
- 105 Ultrashort peptide bioconjugates are exclusively antifungal agents and synergize with cyclodextrin and amphotericin B. Antimicrob. Agents Chemother. 56(1), 1–9 (2012).
- 106 . Ultrashort antibacterial and antifungal lipopeptides. Proc. Natl Acad. Sci. USA 103(43), 15997–16002 (2006).
- 107 . Novel formulations for antimicrobial peptides. Int. J. Mol. Sci. 15(10), 18040–18083 (2014). • Review describing new formulations for improvement of AMPs therapeutic index.
- 108 . Overcoming the challenges in administering biopharmaceuticals: formulation and delivery strategies. Nat. Rev. Drug Discov. 13(9), 655–672 (2014).
- 109 Antifungal nanofibers made by controlled release of sea animal derived peptide. Nanoscale 7(14), 6238–6246 (2015).
- 110 Development and in vivo evaluation of a novel Histatin-5 bioadhesive hydrogel formulation against oral candidiasis. Antimicrob. Agents Chemother. 60(2), 881–889 (2016).
- 111 . Advances in the synthesis of bioactive unnatural amino acids and peptides. Mini Rev. Med. Chem. 12(4), 277–300 (2012).
- 112 . Design, synthesis and antimicrobial properties of non-hemolytic cationic α-cyclopeptoids. Biorg. Med. Chem. 18(5), 2010–2018 (2010).
- 113 . Antifungal properties of peptidomimetics with an arginine-[beta-(2,5,7-tri-tert-butylindol-3-yl)alanine]-arginine motif against Saccharomyces cerevisiae and Zygosaccharomyces bailii. FEMS Yeast Res. 15(3), pii: fov011 (2015).
- 114 . Antifungal activity of 14-helical beta-peptides against planktonic cells and biofilms of Candida species. Pharmaceuticals 8(3), 483–503 (2015).
- 115 . Antimicrobial peptides for therapeutic applications: a review. Molecules 17(10), 12276–12286 (2012).
- 116 . Engineering of a linear inactive analog of human beta-defensin 4 to generate peptides with potent antimicrobial activity. J. Pept. Sci. 21(6), 501–511 (2015).
- 117 . Membrane-active small molecules: designs inspired by antimicrobial peptides. Chem. Med Chem. 10(10), 1606–1624 (2015).
- 118 Cm-p5: an antifungal hydrophilic peptide derived from the coastal mollusk Cenchritis muricatus (Gastropoda: Littorinidae). FASEB J. 29(8), 3315–3325 (2015).
- 119 . Antifungal effect of CopA3 monomer peptide via membrane-active mechanism and stability to proteolysis of enantiomeric D-CopA3. Biochem. Biophys. Res. Commun. 440(1), 94–98 (2013).
- 120 Synthesis and antimicrobial activity of cysteine-free coprisin nonapeptides. Biochem. Biophys. Res. Commun. 443(2), 483–488 (2014).
- 121 Therapeutic efficacy of halocidin-derived peptide HG1 in a mouse model of Candida albicans oral infection. J. Antimicrob. Chemother. 68(5), 1152–1160 (2013).
- 122 . Hb40–61a: novel analogues help expanding the knowledge on chemistry, properties and candidacidal action of this bovine alpha-hemoglobin-derived peptide. Biochim. Biophys. Acta 1848(12), 3140–3149 (2015).
- 123 Killer peptide: a novel paradigm of antimicrobial, antiviral and immunomodulatory auto-delivering drugs. Future Med. Chem. 3(9), 1209–1231 (2011).
- 124 Biological and structural characterization of new linear gomesin analogues with improved therapeutic indices. Biopolymers (Peptide Sci.) 88(3), 386–400 (2007).
- 125 . Improved activity of a synthetic indolicidin analog. Antimicrob. Agents Chemother. 41(4), 771–775 (1997).
- 126 Interaction of antifungal peptide BP15 with Stemphylium vesicarium, the causal agent of brown spot of pear. Fungal Biol. 120(1), 61–71 (2016).
- 127 . Antimicrobial and antibiofilm activity of designed and synthesized antimicrobial peptide, KABT-AMP. Appl. Biochem. Biotechnol. 170(5), 1184–1193 (2013).
- 128 . C. albicans growth, transition, biofilm formation, and gene expression modulation by antimicrobial decapeptide KSL-W. BMC Microbiol. 13(1), 246 (2013).
- 129 Activity of novel synthetic peptides against Candida albicans. Sci. Rep. 5, 9657 (2015).
- 130 . Solution structure of a novel D-naphthylalanine substituted peptide with potential antibacterial and antifungal activities. Biopolymers (Peptide Sci.) 88(5), 738–745 (2007).
- 131 Synthetic β-sheet forming peptide amphiphiles for treatment of fungal keratitis. Biomaterials 43, 44–49 (2015).
- 132 Identification of a novel proline-rich antimicrobial peptide from Brassica napus. PLoS ONE 10(9), e0137414 (2015).
- 133 . Design and studies of multiple mechanism of anti-Candida activity of a new potent Trp-rich peptide dendrimers. Eur. J. Med. Chem. 105, 106–119 (2015).
- 134 . Concentration-dependent mechanisms of cell penetration and killing by the de novo designed antifungal hexapeptide PAF26. Mol. Microbiol. 85(1), 89–106 (2012).
- 135 Concatemerization increases the inhibitory activity of short, cell-penetrating, cationic and tryptophan-rich antifungal peptides. Appl. Microbiol. Biotechnol. 99(19), 8011–8021 (2015).
- 136 . Future directions for peptide therapeutics development. Drug Discov. Today 18(17–18), 807–817 (2013).
- 137 The emergence of peptides in the pharmaceutical business: from exploration to exploitation. EuPA Open Proteomics 4, 58–69 (2014).
- 138 Adis Insight. http://adisinsight.springer.com/.
- 139 . Antimicrobial peptides: therapeutic potentials. Expert Rev. Anti Infect. Ther. 12(12), 1477–1486 (2014).
- 140 . Antifungal peptides: potential candidates for the treatment of fungal infections. Expert Opin. Investig. Drugs 9(2), 273–299 (2000).
- 141 . Combinatorial libraries: a tool to design antimicrobial and antifungal peptide analogues having lytic specificities for structure–activity relationship studies. Biopolymers 55(1), 74–87 (2000).
- 142 . Current trends in antimicrobial agent research: chemo- and bioinformatics approaches. Drug Discov. Today 15(13–14), 540–546 (2010).
- 143 . Structure based virtual screening to discover putative drug candidates: necessary considerations and successful case studies. Methods 71, 135–145 (2015).
- 144 . Treatment of microbial biofilms in the post-antibiotic era: prophylactic and therapeutic use of antimicrobial peptides and their design by bioinformatics tools. Pathog. Dis. 70(3), 257–270 (2014).
- 145 QuBiLs-MAS method in early drug discovery and rational drug identification of antifungal agents. SAR QSAR Environ. Res. 26(11), 943–958 (2015).
- 146 Experimental methodologies and evaluations of computer-aided drug design methodologies applied to a series of 2-aminothiophene derivatives with antifungal activities. Molecules 17(3), 2298–2315 (2012).
- 147 Activity of an antimicrobial peptide mimetic against planktonic and biofilm cultures of oral pathogens. Antimicrob. Agents Chemother. 51(11), 4125–4132 (2007).
- 148 . Peptide array based discovery of synthetic antimicrobial peptides. Front. Microbiol. 4, 402 (2013).
- 149 Rationally designed transmembrane peptide mimics of the multidrug transporter protein Cdr1 act as antagonists to selectively block drug efflux and chemosensitize azole-resistant clinical isolates of Candida albicans. J. Biol. Chem. 288(23), 16775–16787 (2013).
- 150 . Antifungal therapy: drug–drug interactions at your fingertips. J. Antimicrob. Chemother. 71(2), 285–289 (2015).
- 151 . Synthetic antimicrobial beta-peptide in dual-treatment with fluconazole or ketoconazole enhances the in vitro inhibition of planktonic and biofilm Candida albicans. J. Pept. Sci. 21(12), 853–861 (2015).
- 152 . Histatin 5-spermidine conjugates have enhanced fungicidal activity and efficacy as a topical therapeutic for oral candidiasis. Antimicrob. Agents Chemother. 58(2), 756–766 (2014).
- 153 Synthesis of a new peptid–coumarin conjugate: a potential agent against cryptococcosis. ACS Med. Chem. Lett. 6(3), 271–275 (2015).
- 154 . Development of a catheter functionalized by a polydopamine peptide coating with antimicrobial and antibiofilm properties. Acta Biomater. 15, 127–138 (2015).
- 155 Intraluminal release of an antifungal beta-peptide enhances the antifungal and anti-biofilm activities of multilayer-coated catheters in a rat model of venous catheter infection. ACS Biomater. Sci. Eng. 2(1), 112–121 (2016).
- 156 Synthesis and characterization of different immunogenic viral nanoconstructs from rotavirus VP6 inner capsid protein. Int. J. Nanomedicine 9, 2727–2739 (2014).
- 157 . Evolution of antimicrobial peptides to self-assembled peptides for biomaterial applications. Pathogens 3(4), 791–821 (2014).
- 158 The efficacy of self-assembled cationic antimicrobial peptide nanoparticles against Cryptococcus neoformans for the treatment of meningitis. Biomaterials 31(10), 2874–2881 (2010).
- 159 Novel delivery systems for improving the clinical use of peptides. Pharmacol. Rev. 67(3), 541–561 (2015). • Good review on novel controlled peptide delivery systems.