Current state of three-dimensional characterisation of antifungal targets and its use for molecular modelling in drug design

Ringe, 1995, Structure-aided drug design: crystallography and computational approaches, J Nucl Med, 36, 28S Hunter, 1997, A structure-based approach to drug discovery; crystallography and implications for the development of antiparasite drugs, Parasitology, 114, S17, 10.1017/S0031182097008962 Mitchison, 1994, Towards a pharmacological genetics, Chem Biol, 1, 3, 10.1016/1074-5521(94)90034-5 Nielsen, 1994, Combinatorial chemistry, Chem Ind, 22, 902 Vicente, 2003, Microbial natural products as a source of antifungals, Clin Microbiol Infect, 9, 15, 10.1046/j.1469-0691.2003.00489.x Pranav Kumar, 2002, Insights into the selective inhibition of Candida albicans secreted aspartyl protease: a docking analysis study, Bioorg Med Chem, 10, 1153, 10.1016/S0968-0896(01)00385-6 1996 Gschwend, 1996, Molecular docking towards drug discovery, J Mol Recognit, 9, 175, 10.1002/(SICI)1099-1352(199603)9:2<175::AID-JMR260>3.0.CO;2-D Martin, 1992, 3D database searching in drug design, J Med Chem, 35, 2145, 10.1021/jm00090a001 Good, 1995, Three-dimensional structure database searches, Rev Comp Chem, 7, 67 Lewis, 1994, Current methods for site-directed structure generation, J Comput Aided Mol Design, 8, 467, 10.1007/BF00125381 Veselovsky, 2003, Strategy of computer-aided drug design, Curr Drug Targets Infect Disord, 3, 33, 10.2174/1568005033342145 Botta, 2002, Molecular modeling as a powerful technique for understanding small–large molecules interactions, Farmaco, 57, 153, 10.1016/S0014-827X(01)01184-3 Bordas, 2003, Ligand-based computer-aided pesticide design. A review of applications of the CoMFA and CoMSIA methodologies, Pest Manag Sci, 59, 393, 10.1002/ps.614 Dutcher, 1968, The discovery and development of amphotericin B, Dis Chest, 54, 296, 10.1378/chest.54.Supplement_1.296 Ganis, 1971, Polyene macrolide antibiotic amphotericin B. Crystal structure of the N-iodoacetyl derivative, J Am Chem Soc, 93, 4560, 10.1021/ja00747a037 de Kruijff, 1974, Polyene antibiotic–sterol interactions in membranes of Acholeplasma laidlawii cells and lecithin liposomes. III. Molecular structure of the polyene antibiotic–cholesterol complexes, Biochim Biophys Acta, 339, 57, 10.1016/0005-2736(74)90332-0 Baginski, 1997, Molecular properties of amphotericin B membrane channel: a molecular dynamics simulation, Mol Pharmacol, 52, 560, 10.1124/mol.52.4.560 Cotero, 1998, On the role of sterol in the formation of the amphotericin B channel, Biochim Biophys Acta, 1375, 43, 10.1016/S0005-2736(98)00134-5 Baginski, 2002, Comparative molecular dynamics simulations of amphotericin B–cholesterol/ergosterol membrane channels, Biochim Biophys Acta, 1567, 63, 10.1016/S0005-2736(02)00581-3 Brajtburg, 1990, Amphotericin B: current understanding of mechanisms of action, Antimicrob Agents Chemother, 34, 183, 10.1128/AAC.34.2.183 Langlet, 1994, Theoretical study of the complexation of amphotericin B with sterols, Biochim Biophys Acta, 1191, 79, 10.1016/0005-2736(94)90235-6 Caillet, 1995, Theoretical study of the self-association of amphotericin B, Biochim Biophys Acta, 1240, 179, 10.1016/0005-2736(95)00169-7 Gent, 1976, Interaction of the polyene antibiotics with lipid bilayer vesicles containing cholesterol, Biochim Biophys Acta, 426, 17, 10.1016/0005-2736(76)90425-9 Barwicz, 1997, The effect of aggregation state of amphotericin-B on its interactions with cholesterol- or ergosterol-containing phosphatidylcholine monolayers, Chem Phys Lipids, 85, 145, 10.1016/S0009-3084(96)02652-7 Fournier, 1998, The structuring effects of amphotericin B on pure and ergosterol- or cholesterol-containing dipalmitoylphosphatidylcholine bilayers: a differential scanning calorimetry study, Biochim Biophys Acta, 1373, 76, 10.1016/S0005-2736(98)00083-2 Milhaud, 2002, Interactions of the drug amphotericin B with phospholipid membranes containing or not ergosterol: new insight into the role of ergosterol, Biochim Biophys Acta, 1558, 95, 10.1016/S0005-2736(01)00416-3 Paquet, 2002, The effects of amphotericin B on pure and ergosterol- or cholesterol-containing dipalmitoylphosphatidylcholine bilayers as viewed by 2H NMR, Chem Phys Lipids, 119, 1, 10.1016/S0009-3084(02)00071-3 Silberstein, 1997, Conformational analysis of amphotericin B molecule, Membr Cell Biol, 10, 553 Baginski, 1989, Comparative conformational analysis of cholesterol and ergosterol by molecular mechanics, Eur Biophys J, 17, 159, 10.1007/BF00254770 Baran, 2002, Molecular modelling of membrane sterols with the use of the GROMOS 96 force field, Chem Phys Lipids, 120, 21, 10.1016/S0009-3084(02)00106-8 Baran, 2002, Molecular modelling of amphotericin B–ergosterol primary complex in water, Biophys Chem, 95, 125, 10.1016/S0301-4622(01)00252-6 Cheron, 1988, Quantitative structure–activity relationships in amphotericin B derivatives, Biochem Pharmacol, 37, 827, 10.1016/0006-2952(88)90168-2 Cybulska, 2000, N-Methyl-N-d-fructosyl amphotericin B methyl ester (MF-AME), a novel antifungal agent of low toxicity: monomer/micelle control over selective toxicity, Acta Biochim Pol, 47, 121, 10.18388/abp.2000_4069 Parmegiani, 1987, Comparative in vitro and in vivo evaluation of N-d-ornithyl amphotericin B methyl ester, amphotericin B methyl ester, and amphotericin B, Antimicrob Agents Chemother, 31, 1756, 10.1128/AAC.31.11.1756 Maertens, 2004, History of the development of azole derivatives, Clin Microbiol Infect, 10, 1, 10.1111/j.1470-9465.2004.00841.x Heeres, 1979, Antimycotic imidazoles. Part 4. Synthesis and antifungal activity of ketoconazole, a new potent orally active broad-spectrum antifungal agent, J Med Chem, 22, 1003, 10.1021/jm00194a023 Richardson, 1990, Discovery of fluconazole, a novel antifungal agent, Rev Infect Dis, 12, S267, 10.1093/clinids/12.Supplement_3.S267 Gothard, 2004, Voriconazole for serious fungal infections, Int J Clin Pract, 58, 74, 10.1111/j.1368-5031.2004.0099.x Ji, 2000, A three-dimensional model of lanosterol 14alpha-demethylase of Candida albicans and its interaction with azole antifungals, J Med Chem, 43, 2493, 10.1021/jm990589g Ji, 2003, Structure-based de novo design, synthesis, and biological evaluation of non-azole inhibitors specific for lanosterol 14alpha-demethylase of fungi, J Med Chem, 46, 474, 10.1021/jm020362c Slama, 1998, Influence of some novel N-substituted azoles and pyridines on rat hepatic CYP3A activity, Biochem Pharmacol, 55, 1881, 10.1016/S0006-2952(98)00096-3 Höltje, 1998, Construction of a model of the Candida albicans lanosterol 14-alpha-demethylase active site using the homology modelling technique, Pharm Acta Helv, 72, 271, 10.1016/S0031-6865(97)00036-8 Poulos, 1987, High-resolution crystal structure of cytochrome P450cam, J Mol Biol, 195, 687, 10.1016/0022-2836(87)90190-2 Hasemann, 1994, Crystal structure and refinement of cytochrome P450terp at 2.3Ǻ resolution, J Mol Biol, 236, 1169, 10.1016/0022-2836(94)90019-1 Cupp-Vickery, 1995, Structure of cytochrome P450eryF involved in erythromycin biosynthesis, Nat Struct Biol, 2, 144, 10.1038/nsb0295-144 Ravichandran, 1993, Crystal structure of hemoprotein domain of P450BM-3, a prototype for microsomal P450's, Science, 261, 731, 10.1126/science.8342039 Talele, 1997, Docking analysis of a series of cytochrome P-450(14) alpha DM inhibiting azole antifungals, Drug Des Discov, 15, 181 Boscott PE, Grant GH. Modeling cytochrome P450 14 alpha demethylase (Candida albicans) from P450cam. J Mol Graph 1994;12:185–92, 195. Tsukuda, 1998, Modeling, synthesis and biological activity of novel antifungal agents (1), Bioorg Med Chem Lett, 8, 1819, 10.1016/S0960-894X(98)00316-3 Hasemann, 1995, Structure and function of cytochromes P450: a comparative analysis of three crystal structures, Structure, 3, 41, 10.1016/S0969-2126(01)00134-4 Lewis, 1999, Molecular modelling of lanosterol 14 alpha-demethylase (CYP51) from Saccharomyces cerevisiae via homology with CYP102, a unique bacterial cytochrome P450 isoform: quantitative structure–activity relationships (QSARs) within two related series of antifungal azole derivatives, J Enzyme Inhib, 14, 175, 10.3109/14756369909030315 Podust, 2001, Crystal structure of cytochrome P450 14alpha-sterol demethylase (CYP51) from Mycobacterium tuberculosis in complex with azole inhibitors, Proc Natl Acad Sci USA, 98, 3068, 10.1073/pnas.061562898 Podust, 2001, Substrate recognition sites in 14alpha-sterol demethylase from comparative analysis of amino acid sequences and X-ray structure of Mycobacterium tuberculosis CYP51, J Inorg Biochem, 87, 227, 10.1016/S0162-0134(01)00388-9 Xiao, 2004, Three-dimensional models of wild-type and mutated forms of cytochrome P450 14alpha-sterol demethylases from Aspergillus fumigatus and Candida albicans provide insights into posaconazole binding, Antimicrob Agents Chemother, 48, 568, 10.1128/AAC.48.2.568-574.2004 Fukuoka, 2003, Genetic basis for differential activities of fluconazole and voriconazole against Candida krusei, Antimicrob Agents Chemother, 47, 1213, 10.1128/AAC.47.4.1213-1219.2003 Mieth, 1990, The early development of allylamine antimycotics, J Dermatolog Treat, 1, 5, 10.3109/09546639009089021 Leitner K-H, editor. Von der Idee zum Markt: Die 50 besten Innovationen Österreichs. Erfolgsgeschichten der österreichischen Industrie zwischen 1975 und 2000. Wien: Böhlau Verlag; 2003. Nussbaumer, 1993, Synthesis and structure–activity relationships of naphthalene-substituted derivatives of the allylamine antimycotic terbinafine, J Med Chem, 36, 2810, 10.1021/jm00071a011 Nussbaumer, 1991, Synthesis and structure–activity relationships of benzo[b]thienylallylamine antimycotics, J Med Chem, 34, 65, 10.1021/jm00105a011 Nussbaumer, 1994, Synthesis and structure–activity relationships of the novel homopropargylamine antimycotics, J Med Chem, 37, 610, 10.1021/jm00031a010 Nussbaumer, 1995, Synthesis and structure–activity relationships of side-chain-substituted analogs of the allylamine antimycotic terbinafine lacking the central amino function, J Med Chem, 38, 1831, 10.1021/jm00010a029 Favre, 1996, Characterisation of squalene epoxidase activity from the dermatophyte Trichophyton rubrum and its inhibition by terbinafine and other antimycotic agents, Antimicrob Agents Chemother, 40, 443, 10.1128/AAC.40.2.443 Ryder, 1992, Terbinafine: mode of action and properties of the squalene epoxidase inhibition, Br J Dermatol, 126, 2, 10.1111/j.1365-2133.1992.tb00001.x Gokhale, 1999, Comparative molecular field analysis of fungal squalene epoxidase inhibitors, J Med Chem, 42, 5348, 10.1021/jm9806852 Favre, 1997, Differential inhibition of fungal and mammalian squalene epoxidases by the benzylamine SDZ SBA 586 in comparison with the allylamine terbinafine, Arch Biochem Biophys, 340, 265, 10.1006/abbi.1997.9908 Gokhale, 2000, Understanding the antifungal activity of terbinafine analogues using quantitative structure–activity relationship (QSAR) models, Bioorg Med Chem, 8, 2487, 10.1016/S0968-0896(00)00178-4 Georgopapadakou, 1996, Antifungal agents: chemotherapeutic targets and immunologic strategies, Antimicrob Agents Chemother, 40, 279, 10.1128/AAC.40.2.279 Haria, 1995, Amorolfine. A review of its pharmacological properties and therapeutic potential in the treatment of onychomycosis and other superficial fungal infections, Drugs, 49, 103, 10.2165/00003495-199549010-00008 Polak, 1988, Mode of action of morpholine derivatives, Ann NY Acad Sci, 544, 221, 10.1111/j.1749-6632.1988.tb40406.x Keon, 1994, Isolation of the ERG2 gene, encoding sterol delta 8 → delta 7 isomerase, from the rice blast fungus Magnaporthe grisea and its expression in the maize smut pathogen Ustilago maydis, Curr Genet, 25, 531, 10.1007/BF00351674 Lai, 1994, The identification of a gene family in the Saccharomyces cerevisiae ergosterol biosynthesis pathway, Gene, 140, 41, 10.1016/0378-1119(94)90728-5 Smith, 1995, Cloning and sequence analysis of an ERG24 homolog from Schizosaccharomyces pombe, Gene, 155, 139, 10.1016/0378-1119(94)00902-5 1999 Bracher, 2001, Medikamentöse Behandlung von lokalen Pilzinfektionen — Flucytosin Ireton, 2002, The structure of Escherichia coli cytosine deaminase, J Mol Biol, 315, 687, 10.1006/jmbi.2001.5277 Ireton, 2003, The 1.14Å crystal structure of yeast cytosine deaminase: evolution of nucleotide salvage enzymes and implications for genetic chemotherapy, Structure (Camb), 11, 961, 10.1016/S0969-2126(03)00153-9 Ko, 2003, Crystal structure of yeast cytosine deaminase. Insights into enzyme mechanism and evolution, J Biol Chem, 278, 19111, 10.1074/jbc.M300874200 Oxford, 1939, Griseofulvin, C17H17O6Cl, a metabolic product of Penicillium griseofulvum Dierks, Biochem J, 33, 240, 10.1042/bj0330240 Develoux, 2001, Griseofulvin, Ann Dermatol Venereol, 128, 1317 De Carli, 1988, Griseofulvin, Mutat Res, 195, 91, 10.1016/0165-1110(88)90020-6 Weber, 1976, Griseofulvin interacts with microtubules both in vivo and in vitro, J Mol Biol, 102, 817, 10.1016/0022-2836(76)90293-X Roobol, 1976, Inhibition by griseofulvin of microtubule assembly in vitro, FEBS Lett, 67, 248, 10.1016/0014-5793(76)80539-X Keates, 1981, Griseofulvin at low concentration inhibits the rate of microtubule polymerization in vitro, Biochem Biophys Res Commun, 102, 746, 10.1016/S0006-291X(81)80195-7 Sloboda, 1982, Griseofulvin: association with tubulin and inhibition of in vitro microtubule assembly, Biochem Biophys Res Commun, 105, 882, 10.1016/0006-291X(82)91052-X Sato, 1984, Viscometric and electron microscopic analysis of effects of griseofulvin and its derivatives on in vitro polymerization of microtubule proteins and depolymerization of microtubules, J Pharmacobiodyn, 7, 156, 10.1248/bpb1978.7.156 Takeuchi, 1997, Syntheses and antifungal activity of dl-griseofulvin and its congeners. III, Chem Pharm Bull (Tokyo), 45, 2011, 10.1248/cpb.45.2011 Friedrich, 1996, Sulfogriseofulvin derivatives. Synthesis by [4+2]cycloaddition, structure, properties, crystal structure analysis, and antifungal activity of spiro[1,3-benzoxathiole-2,1′-cyclohex-2′-en]-4′-one 3,3-dioxides, Arch Pharm (Weinheim), 329, 361, 10.1002/ardp.19963290706 Lila, 2003, Molecular basis for fungal selectivity of novel antimitotic compounds, Antimicrob Agents Chemother, 47, 2273, 10.1128/AAC.47.7.2273-2282.2003 Lowe, 2001, Refined structure of alpha beta-tubulin at 3.5Å resolution, J Mol Biol, 313, 1045, 10.1006/jmbi.2001.5077 Kiso, 2004, Screening for microtubule-disrupting antifungal agents by using a mitotic-arrest mutant of Aspergillus nidulans and novel action of phenylalanine derivatives accompanying tubulin loss, Antimicrob Agents Chemother, 48, 1739, 10.1128/AAC.48.5.1739-1748.2004 Kurtz, 1998, New antifungal drug targets: a vision for the future, ASM News, 64, 31 Goldman, 1995, Antifungal drug targets: Candida secreted aspartyl protease and fungal wall beta-glucan synthesis, Infect Agents Dis, 4, 228 Liu, 2001, 1,3-beta-Glucan synthase: a useful target for antifungal drugs, Curr Drug Targets Infect Disord, 1, 159, 10.2174/1568005014606107 Douglas, 1994, The Saccharomyces cerevisiae FKS1 (ETG1) gene encodes an integral membrane protein which is a subunit of 1,3-beta-d-glucan synthase, Proc Natl Acad Sci USA, 91, 12907, 10.1073/pnas.91.26.12907 Mazur, 1995, Differential expression and function of two homologous subunits of yeast 1,3-beta-d-glucan synthase, Mol Cell Biol, 15, 5671, 10.1128/MCB.15.10.5671 Kelly, 1996, Isolation of a gene involved in 1,3-beta-glucan synthesis in Aspergillus nidulans and purification of the corresponding protein, J Bacteriol, 178, 4381, 10.1128/jb.178.15.4381-4391.1996 Douglas, 1997, Identification of the FKS1 gene of Candida albicans as the essential target of 1,3-beta-d-glucan synthase inhibitors, Antimicrob Agents Chemother, 41, 2471, 10.1128/AAC.41.11.2471 Thompson, 1999, A glucan synthase FKS1 homolog in Cryptococcus neoformans is single copy and encodes an essential function, J Bacteriol, 181, 444, 10.1128/JB.181.2.444-453.1999 Pereira, 2000, Molecular cloning and characterisation of a glucan synthase gene from the human pathogenic fungus Paracoccidioides brasiliensis, Yeast, 16, 451, 10.1002/(SICI)1097-0061(20000330)16:5<451::AID-YEA540>3.0.CO;2-O Beauvais, 2001, Glucan synthase complex of Aspergillus fumigatus, J Bacteriol, 183, 2273, 10.1128/JB.183.7.2273-2279.2001 Schimoler-O’Rourke, 2003, Neurospora crassa FKS protein binds to the (1,3)beta-glucan synthase substrate, UDP-glucose, Curr Microbiol, 46, 408, 10.1007/s00284-002-3884-5 Sipos, 1993, Predicting the topology of eukaryotic membrane proteins, Eur J Biochem, 213, 1333, 10.1111/j.1432-1033.1993.tb17885.x Douglas, 2001, Fungal beta(1,3)-d-glucan synthesis, Med Mycol, 39, 55, 10.1080/mmy.39.1.55.66 Nyfeler, 1974, Metabolites of microorganisms. 143. Echinocandin B, a novel polypeptide-antibiotic from Aspergillus nidulans var. echinulatus: isolation and structural components, Helv Chim Acta, 57, 2459, 10.1002/hlca.19740570818 Onishi, 2000, Discovery of novel antifungal (1,3)-beta-d-glucan synthase inhibitors, Antimicrob Agents Chemother, 44, 368, 10.1128/AAC.44.2.368-377.2000 Debono, 1994, Antibiotics that inhibit fungal cell wall development, Annu Rev Microbiol, 48, 471, 10.1146/annurev.mi.48.100194.002351 Schmatz, 1992, Pneumocandins from Zalerion arboricola. IV. Biological evaluation of natural and semisynthetic pneumocandins for activity against Pneumocystis carinii and Candida species, J Antibiot (Tokyo), 45, 1886, 10.7164/antibiotics.45.1886 Kurtz, 1994, Increased antifungal activity of L-733,560, a water-soluble, semisynthetic pneumocandin, is due to enhanced inhibition of cell wall synthesis, Antimicrob Agents Chemother, 38, 2750, 10.1128/AAC.38.12.2750 Schmatz, 1995, New semisynthetic pneumocandins with improved efficacies against Pneumocystis carinii in the rat, Antimicrob Agents Chemother, 39, 1320, 10.1128/AAC.39.6.1320 Masubuchi, 2001, Synthesis and antifungal activities of novel 1,3-beta-d-glucan synthase inhibitors. Part 1, Bioorg Med Chem Lett, 11, 395, 10.1016/S0960-894X(00)00678-8 Masubuchi, 2001, Synthesis and antifungal activities of novel 1,3-beta-d-glucan synthase inhibitors. Part 2, Bioorg Med Chem Lett, 11, 1273, 10.1016/S0960-894X(01)00178-0 Odds, 2003, Antifungal agents: mechanisms of action, Trends Microbiol, 11, 272, 10.1016/S0966-842X(03)00117-3 Barrett, 2002, From natural products to clinically useful antifungals, Biochim Biophys Acta, 1587, 224, 10.1016/S0925-4439(02)00085-6 Denning, 2003, Echinocandin antifungal drugs, Lancet, 362, 1142, 10.1016/S0140-6736(03)14472-8 Pelaez, 2000, The discovery of enfumafungin, a novel antifungal compound produced by an endophytic Hormonema species, biological activity and taxonomy of the producing organisms, Syst Appl Microbiol, 23, 333, 10.1016/S0723-2020(00)80062-4 Kurtz, 1997, Lipopeptide inhibitors of fungal glucan synthase, J Med Vet Mycol, 35, 79, 10.1080/02681219780000961 Ohyama, 2004, FKS1 mutations responsible for selective resistance of Saccharomyces cerevisiae to the novel 1,3-beta-glucan synthase inhibitor arborcandin C, Antimicrob Agents Chemother, 48, 319, 10.1128/AAC.48.1.319-322.2004 Douglas, 1994, A Saccharomyces cerevisiae mutant with echinocandin-resistant 1,3-beta-d-glucan synthase, J Bacteriol, 176, 5686, 10.1128/jb.176.18.5686-5696.1994 Capa, 1998, Translation elongation factor 2 is part of the target for a new family of antifungals, Antimicrob Agents Chemother, 42, 2694, 10.1128/AAC.42.10.2694 Chakraburtty, 1998, Yeast elongation factor 3: structure and function, Biol Chem, 379, 831, 10.1515/bchm.1998.379.7.831 Justice, 1998, Elongation factor 2 as a novel target for selective inhibition of fungal protein synthesis, J Biol Chem, 273, 3148, 10.1074/jbc.273.6.3148 Fostel, 2000, Emerging novel antifungal agents, Drug Discov Today, 5, 25, 10.1016/S1359-6446(99)01430-0 Czworkowski, 1994, The crystal structure of elongation factor G complexed with GDP, at 2.7Å resolution, EMBO J, 13, 3661, 10.1002/j.1460-2075.1994.tb06675.x AEvarsson, 1994, Three-dimensional structure of the ribosomal translocase: elongation factor G from Thermus thermophilus, EMBO J, 13, 3669, 10.1002/j.1460-2075.1994.tb06676.x Futterer, 2001, Crystallographic phasing of myristoyl-CoA-protein N-myristoyltransferase using an iodinated analog of myristoyl-CoA, Acta Crystallogr D Biol Crystallogr, 57, 393, 10.1107/S090744490100052X Georgopapadakou, 2002, Antifungals targeted to protein modification: focus on protein N-myristoyltransferase, Expert Opin Investig Drugs, 11, 1117, 10.1517/13543784.11.8.1117 Weston, 1998, Crystal structure of the anti-fungal target N-myristoyl transferase, Nat Struct Biol, 5, 213, 10.1038/nsb0398-213 Sogabe, 2002, Crystal structures of Candida albicans N-myristoyltransferase with two distinct inhibitors, Chem Biol, 9, 1119, 10.1016/S1074-5521(02)00240-5 Karki, 2001, A feature based pharmacophore for Candida albicans MyristoylCoA: protein N-myristoyltransferase inhibitors, Eur J Med Chem, 36, 147, 10.1016/S0223-5234(00)01202-2 Ebiike, 2002, Design and synthesis of novel benzofurans as a new class of antifungal agents targeting fungal N-myristoyltransferase. Part 2, Bioorg Med Chem Lett, 12, 607, 10.1016/S0960-894X(01)00808-3 Kawasaki, 2003, Design and synthesis of novel benzofurans as a new class of antifungal agents targeting fungal N-myristoyltransferase. Part 3, Bioorg Med Chem Lett, 13, 87, 10.1016/S0960-894X(02)00844-2 Purushottamachar, 2003, 3D-QSAR of N-myristoyltransferase inhibiting antifungal agents by CoMFA and CoMSIA methods, Bioorg Med Chem, 11, 3487, 10.1016/S0968-0896(03)00305-5 Hube, 2001, Candida albicans proteinases: resolving the mystery of a gene family, Microbiology, 147, 1997, 10.1099/00221287-147-8-1997 Schaller, 2003, The secreted aspartyl proteinases Sap1 and Sap2 cause tissue damage in an in vitro model of vaginal candidiasis based on reconstituted human vaginal epithelium, Infect Immun, 71, 3227, 10.1128/IAI.71.6.3227-3234.2003 Cutfield, 1993, Crystallization of inhibited aspartic proteinase from Candida albicans, J Mol Biol, 234, 1266, 10.1006/jmbi.1993.1679 Stewart, 2001, Candida proteases and their inhibition: prospects for antifungal therapy, Curr Med Chem, 8, 941, 10.2174/0929867013372698 Cutfield, 1995, The crystal structure of a major secreted aspartic proteinase from Candida albicans in complexes with two inhibitors, Structure, 3, 1261, 10.1016/S0969-2126(01)00261-1 Abad-Zapatero, 1996, Structure of a secreted aspartic protease from C. albicans complexed with a potent inhibitor: implications for the design of antifungal agents, Protein Sci, 5, 640, 10.1002/pro.5560050408 Symersky, 1997, High-resolution structure of the extracellular aspartic proteinase from Candida tropicalis yeast, Biochemistry, 36, 12700, 10.1021/bi970613x Nicholls, 1991, Protein folding and association: insights from the interfacial and thermodynamic properties of hydrocarbons, Proteins, 11, 281, 10.1002/prot.340110407 Naglik, 2003, Candida albicans secreted aspartyl proteinases in virulence and pathogenesis, Microbiol Mol Biol Rev, 67, 400, 10.1128/MMBR.67.3.400-428.2003 Hoegl, 1999, Inhibitors of aspartic proteases in human diseases: molecular modeling comes of age, Pharmazie, 54, 319 Abad-Zapatero, 1998, Structure of secreted aspartic proteinases from Candida. Implications for the design of antifungal agents, Adv Exp Med Biol, 436, 297, 10.1007/978-1-4615-5373-1_41 Koelsch, 2000, Enzymic characteristics of secreted aspartic proteases of Candida albicans, Biochim Biophys Acta, 1480, 117, 10.1016/S0167-4838(00)00068-6 Pichova, 2001, Secreted aspartic proteases of Candida albicans, Candida tropicalis, Candida parapsilosis and Candida lusitaniae. Inhibition with peptidomimetic inhibitors, Eur J Biochem, 268, 2669, 10.1046/j.1432-1327.2001.02152.x