JP2002541066A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2002541066A5 JP2002541066A5 JP2000599777A JP2000599777A JP2002541066A5 JP 2002541066 A5 JP2002541066 A5 JP 2002541066A5 JP 2000599777 A JP2000599777 A JP 2000599777A JP 2000599777 A JP2000599777 A JP 2000599777A JP 2002541066 A5 JP2002541066 A5 JP 2002541066A5
- Authority
- JP
- Japan
- Prior art keywords
- polypeptide
- endotoxin
- antimicrobial
- activity
- kda
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 108090000765 processed proteins & peptides Proteins 0.000 description 300
- 229920001184 polypeptide Polymers 0.000 description 295
- 102000004196 processed proteins & peptides Human genes 0.000 description 295
- 239000002158 endotoxin Substances 0.000 description 181
- CSSYQJWUGATIHM-IKGCZBKSSA-N l-phenylalanyl-l-lysyl-l-cysteinyl-l-arginyl-l-arginyl-l-tryptophyl-l-glutaminyl-l-tryptophyl-l-arginyl-l-methionyl-l-lysyl-l-lysyl-l-leucylglycyl-l-alanyl-l-prolyl-l-seryl-l-isoleucyl-l-threonyl-l-cysteinyl-l-valyl-l-arginyl-l-arginyl-l-alanyl-l-phenylal Chemical compound C([C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 CSSYQJWUGATIHM-IKGCZBKSSA-N 0.000 description 146
- 108010063045 Lactoferrin Proteins 0.000 description 131
- 102000010445 Lactoferrin Human genes 0.000 description 131
- 229940078795 lactoferrin Drugs 0.000 description 128
- 235000021242 lactoferrin Nutrition 0.000 description 128
- 235000001014 amino acid Nutrition 0.000 description 91
- 230000000845 anti-microbial effect Effects 0.000 description 86
- 229940024606 amino acid Drugs 0.000 description 85
- 150000001413 amino acids Chemical class 0.000 description 85
- 210000004027 cell Anatomy 0.000 description 76
- 230000000694 effects Effects 0.000 description 57
- 239000012634 fragment Substances 0.000 description 51
- 241000282414 Homo sapiens Species 0.000 description 43
- 229920006008 lipopolysaccharide Polymers 0.000 description 41
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 38
- 230000003472 neutralizing effect Effects 0.000 description 38
- 238000006467 substitution reaction Methods 0.000 description 35
- 238000002474 experimental method Methods 0.000 description 32
- 102000003908 Cathepsin D Human genes 0.000 description 31
- 108090000258 Cathepsin D Proteins 0.000 description 31
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 30
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 30
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 30
- 239000003814 drug Substances 0.000 description 30
- 230000012010 growth Effects 0.000 description 28
- GZQKNULLWNGMCW-PWQABINMSA-N lipid A (E. coli) Chemical compound O1[C@H](CO)[C@@H](OP(O)(O)=O)[C@H](OC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCCCC)[C@@H](NC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCC)[C@@H]1OC[C@@H]1[C@@H](O)[C@H](OC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](NC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](OP(O)(O)=O)O1 GZQKNULLWNGMCW-PWQABINMSA-N 0.000 description 28
- 238000000034 method Methods 0.000 description 28
- 239000000047 product Substances 0.000 description 28
- 241000588724 Escherichia coli Species 0.000 description 27
- 230000000813 microbial effect Effects 0.000 description 27
- 230000007123 defense Effects 0.000 description 26
- 210000002966 serum Anatomy 0.000 description 26
- 244000005700 microbiome Species 0.000 description 25
- 230000027455 binding Effects 0.000 description 24
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 22
- 229920000669 heparin Polymers 0.000 description 22
- 229960002897 heparin Drugs 0.000 description 22
- 102000035195 Peptidases Human genes 0.000 description 20
- 108091005804 Peptidases Proteins 0.000 description 20
- 239000004365 Protease Substances 0.000 description 20
- 238000001727 in vivo Methods 0.000 description 20
- 230000001965 increasing effect Effects 0.000 description 19
- 208000015181 infectious disease Diseases 0.000 description 19
- 239000012528 membrane Substances 0.000 description 19
- 239000011780 sodium chloride Substances 0.000 description 19
- 241001465754 Metazoa Species 0.000 description 18
- 241000894006 Bacteria Species 0.000 description 17
- 229920002683 Glycosaminoglycan Polymers 0.000 description 17
- 230000000875 corresponding effect Effects 0.000 description 17
- 125000003275 alpha amino acid group Chemical group 0.000 description 16
- 230000029087 digestion Effects 0.000 description 15
- 229940079593 drug Drugs 0.000 description 15
- 102000005600 Cathepsins Human genes 0.000 description 14
- 108010084457 Cathepsins Proteins 0.000 description 14
- 230000001580 bacterial effect Effects 0.000 description 14
- 230000005764 inhibitory process Effects 0.000 description 14
- 238000012360 testing method Methods 0.000 description 14
- 210000001519 tissue Anatomy 0.000 description 14
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 13
- 102000057297 Pepsin A Human genes 0.000 description 13
- 108090000284 Pepsin A Proteins 0.000 description 13
- 210000000440 neutrophil Anatomy 0.000 description 13
- 229940111202 pepsin Drugs 0.000 description 13
- 235000018102 proteins Nutrition 0.000 description 13
- 102000004169 proteins and genes Human genes 0.000 description 13
- 108090000623 proteins and genes Proteins 0.000 description 13
- 230000028327 secretion Effects 0.000 description 13
- 208000035143 Bacterial infection Diseases 0.000 description 12
- 208000022362 bacterial infectious disease Diseases 0.000 description 12
- 239000000203 mixture Substances 0.000 description 12
- 239000002253 acid Substances 0.000 description 11
- 239000004599 antimicrobial Substances 0.000 description 11
- 238000003556 assay Methods 0.000 description 11
- 230000003115 biocidal effect Effects 0.000 description 11
- -1 iron ion Chemical class 0.000 description 11
- 239000002609 medium Substances 0.000 description 11
- 210000001616 monocyte Anatomy 0.000 description 11
- 230000002829 reductive effect Effects 0.000 description 11
- 150000003839 salts Chemical class 0.000 description 11
- 230000002378 acidificating effect Effects 0.000 description 10
- 125000001931 aliphatic group Chemical group 0.000 description 10
- 230000007893 endotoxin activity Effects 0.000 description 10
- 108020001507 fusion proteins Proteins 0.000 description 10
- 102000037865 fusion proteins Human genes 0.000 description 10
- 230000002401 inhibitory effect Effects 0.000 description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 10
- 235000019419 proteases Nutrition 0.000 description 10
- 239000000523 sample Substances 0.000 description 10
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 9
- 108010023063 Bacto-peptone Proteins 0.000 description 9
- 108010093965 Polymyxin B Proteins 0.000 description 9
- 231100000673 dose–response relationship Toxicity 0.000 description 9
- 230000006870 function Effects 0.000 description 9
- 230000002209 hydrophobic effect Effects 0.000 description 9
- 229920000024 polymyxin B Polymers 0.000 description 9
- 229960005266 polymyxin b Drugs 0.000 description 9
- JQXXHWHPUNPDRT-WLSIYKJHSA-N rifampicin Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)NC=2C(O)=C3C([O-])=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N1CC[NH+](C)CC1 JQXXHWHPUNPDRT-WLSIYKJHSA-N 0.000 description 9
- 229960001225 rifampicin Drugs 0.000 description 9
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 8
- 239000003242 anti bacterial agent Substances 0.000 description 8
- 238000009472 formulation Methods 0.000 description 8
- 239000001963 growth medium Substances 0.000 description 8
- 238000003119 immunoblot Methods 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- 241000239218 Limulus Species 0.000 description 7
- 241000699666 Mus <mouse, genus> Species 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 7
- 238000010790 dilution Methods 0.000 description 7
- 239000012895 dilution Substances 0.000 description 7
- 230000002121 endocytic effect Effects 0.000 description 7
- 229910052742 iron Inorganic materials 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 230000007246 mechanism Effects 0.000 description 7
- 238000006386 neutralization reaction Methods 0.000 description 7
- 239000002953 phosphate buffered saline Substances 0.000 description 7
- 238000012545 processing Methods 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 230000001629 suppression Effects 0.000 description 7
- 238000002965 ELISA Methods 0.000 description 6
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 6
- 125000002091 cationic group Chemical group 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 230000002757 inflammatory effect Effects 0.000 description 6
- 230000002132 lysosomal effect Effects 0.000 description 6
- 238000010172 mouse model Methods 0.000 description 6
- 229920000447 polyanionic polymer Polymers 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 201000008827 tuberculosis Diseases 0.000 description 6
- 239000007995 HEPES buffer Substances 0.000 description 5
- 206010061218 Inflammation Diseases 0.000 description 5
- 150000001408 amides Chemical class 0.000 description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
- 238000005119 centrifugation Methods 0.000 description 5
- 238000005345 coagulation Methods 0.000 description 5
- 230000015271 coagulation Effects 0.000 description 5
- 210000003022 colostrum Anatomy 0.000 description 5
- 235000021277 colostrum Nutrition 0.000 description 5
- 230000007423 decrease Effects 0.000 description 5
- 230000004054 inflammatory process Effects 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- 239000007928 intraperitoneal injection Substances 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 230000001681 protective effect Effects 0.000 description 5
- 230000002797 proteolythic effect Effects 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 238000011870 unpaired t-test Methods 0.000 description 5
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 4
- 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 239000004471 Glycine Substances 0.000 description 4
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 4
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 4
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 4
- 238000011050 LAL assay Methods 0.000 description 4
- 241000186359 Mycobacterium Species 0.000 description 4
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 229920001586 anionic polysaccharide Polymers 0.000 description 4
- 150000004836 anionic polysaccharides Chemical class 0.000 description 4
- 230000001986 anti-endotoxic effect Effects 0.000 description 4
- 229940088710 antibiotic agent Drugs 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 238000003501 co-culture Methods 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 229940088598 enzyme Drugs 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 210000000416 exudates and transudate Anatomy 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 230000009422 growth inhibiting effect Effects 0.000 description 4
- 125000001165 hydrophobic group Chemical group 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 238000007912 intraperitoneal administration Methods 0.000 description 4
- 201000002364 leukopenia Diseases 0.000 description 4
- 231100001022 leukopenia Toxicity 0.000 description 4
- 210000002540 macrophage Anatomy 0.000 description 4
- 230000035699 permeability Effects 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 229920001282 polysaccharide Polymers 0.000 description 4
- 239000005017 polysaccharide Substances 0.000 description 4
- 150000004804 polysaccharides Chemical class 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- 230000017854 proteolysis Effects 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 230000035945 sensitivity Effects 0.000 description 4
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
- 238000012546 transfer Methods 0.000 description 4
- 239000004474 valine Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- MSWZFWKMSRAUBD-GASJEMHNSA-N 2-amino-2-deoxy-D-galactopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O MSWZFWKMSRAUBD-GASJEMHNSA-N 0.000 description 3
- 241000186361 Actinobacteria <class> Species 0.000 description 3
- 108700042778 Antimicrobial Peptides Proteins 0.000 description 3
- 102000044503 Antimicrobial Peptides Human genes 0.000 description 3
- 239000004475 Arginine Substances 0.000 description 3
- 102000035101 Aspartic proteases Human genes 0.000 description 3
- 108091005502 Aspartic proteases Proteins 0.000 description 3
- 101100505161 Caenorhabditis elegans mel-32 gene Proteins 0.000 description 3
- 206010017533 Fungal infection Diseases 0.000 description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
- 206010024229 Leprosy Diseases 0.000 description 3
- 108010028921 Lipopeptides Proteins 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 208000031888 Mycoses Diseases 0.000 description 3
- 206010036790 Productive cough Diseases 0.000 description 3
- 229920002684 Sepharose Polymers 0.000 description 3
- 206010040047 Sepsis Diseases 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000005862 Whey Substances 0.000 description 3
- 102000007544 Whey Proteins Human genes 0.000 description 3
- 108010046377 Whey Proteins Proteins 0.000 description 3
- 238000005273 aeration Methods 0.000 description 3
- 235000004279 alanine Nutrition 0.000 description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 3
- 201000005008 bacterial sepsis Diseases 0.000 description 3
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 210000001124 body fluid Anatomy 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 210000004899 c-terminal region Anatomy 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 238000011260 co-administration Methods 0.000 description 3
- 239000012228 culture supernatant Substances 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- 238000012744 immunostaining Methods 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 229960003350 isoniazid Drugs 0.000 description 3
- QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 description 3
- 210000000265 leukocyte Anatomy 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 239000006166 lysate Substances 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 108010091212 pepstatin Proteins 0.000 description 3
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 3
- 210000001539 phagocyte Anatomy 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 239000012723 sample buffer Substances 0.000 description 3
- 238000013207 serial dilution Methods 0.000 description 3
- 210000003802 sputum Anatomy 0.000 description 3
- 208000024794 sputum Diseases 0.000 description 3
- AZKSAVLVSZKNRD-UHFFFAOYSA-M 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide Chemical compound [Br-].S1C(C)=C(C)N=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 AZKSAVLVSZKNRD-UHFFFAOYSA-M 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- 229920000936 Agarose Polymers 0.000 description 2
- 102000004580 Aspartic Acid Proteases Human genes 0.000 description 2
- 108010017640 Aspartic Acid Proteases Proteins 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 201000003883 Cystic fibrosis Diseases 0.000 description 2
- 108010092160 Dactinomycin Proteins 0.000 description 2
- 238000000729 Fisher's exact test Methods 0.000 description 2
- 239000012981 Hank's balanced salt solution Substances 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 108091092195 Intron Proteins 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- 101800004361 Lactoferricin-B Proteins 0.000 description 2
- 101800004366 Lactoferricin-H Proteins 0.000 description 2
- 102400000839 Lactoferricin-H Human genes 0.000 description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- 208000032376 Lung infection Diseases 0.000 description 2
- 102000008072 Lymphokines Human genes 0.000 description 2
- 108010074338 Lymphokines Proteins 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 241000018377 Methylococcaceae bacterium Species 0.000 description 2
- 241000187480 Mycobacterium smegmatis Species 0.000 description 2
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 2
- 241000588650 Neisseria meningitidis Species 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- 108090000783 Renin Proteins 0.000 description 2
- 102100028255 Renin Human genes 0.000 description 2
- 206010040070 Septic Shock Diseases 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 239000013504 Triton X-100 Substances 0.000 description 2
- 229920004890 Triton X-100 Polymers 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 2
- 230000030833 cell death Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 238000011109 contamination Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 229960000640 dactinomycin Drugs 0.000 description 2
- 238000000326 densiometry Methods 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 239000006196 drop Substances 0.000 description 2
- 238000001962 electrophoresis Methods 0.000 description 2
- 230000009881 electrostatic interaction Effects 0.000 description 2
- 230000001159 endocytotic effect Effects 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 239000012847 fine chemical Substances 0.000 description 2
- 230000037406 food intake Effects 0.000 description 2
- 235000013882 gravy Nutrition 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 235000020256 human milk Nutrition 0.000 description 2
- 210000004251 human milk Anatomy 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 239000002054 inoculum Substances 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
- 229960000310 isoleucine Drugs 0.000 description 2
- 230000002147 killing effect Effects 0.000 description 2
- 230000001665 lethal effect Effects 0.000 description 2
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- 239000012139 lysis buffer Substances 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 238000000816 matrix-assisted laser desorption--ionisation Methods 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 244000000010 microbial pathogen Species 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 239000008267 milk Substances 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 150000002482 oligosaccharides Polymers 0.000 description 2
- 229940037201 oris Drugs 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N phosphoric acid Substances OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 230000004962 physiological condition Effects 0.000 description 2
- 238000007747 plating Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000005180 public health Effects 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 230000036303 septic shock Effects 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 230000001568 sexual effect Effects 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- 239000003656 tris buffered saline Substances 0.000 description 2
- CBOJBBMQJBVCMW-NQZVPSPJSA-N (2r,3r,4r,5r)-2-amino-3,4,5,6-tetrahydroxyhexanal;hydrochloride Chemical compound Cl.O=C[C@H](N)[C@@H](O)[C@@H](O)[C@H](O)CO CBOJBBMQJBVCMW-NQZVPSPJSA-N 0.000 description 1
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- AXAVXPMQTGXXJZ-UHFFFAOYSA-N 2-aminoacetic acid;2-amino-2-(hydroxymethyl)propane-1,3-diol Chemical compound NCC(O)=O.OCC(N)(CO)CO AXAVXPMQTGXXJZ-UHFFFAOYSA-N 0.000 description 1
- ZSLUVFAKFWKJRC-IGMARMGPSA-N 232Th Chemical compound [232Th] ZSLUVFAKFWKJRC-IGMARMGPSA-N 0.000 description 1
- QRXMUCSWCMTJGU-UHFFFAOYSA-N 5-bromo-4-chloro-3-indolyl phosphate Chemical compound C1=C(Br)C(Cl)=C2C(OP(O)(=O)O)=CNC2=C1 QRXMUCSWCMTJGU-UHFFFAOYSA-N 0.000 description 1
- 101150037123 APOE gene Proteins 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 208000031729 Bacteremia Diseases 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 102000004178 Cathepsin E Human genes 0.000 description 1
- 108090000611 Cathepsin E Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 108090000746 Chymosin Proteins 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 101100216294 Danio rerio apoeb gene Proteins 0.000 description 1
- 108010002069 Defensins Proteins 0.000 description 1
- 102000000541 Defensins Human genes 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 206010013710 Drug interaction Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 101100379081 Emericella variicolor andC gene Proteins 0.000 description 1
- 241000097983 Escherichia coli O113 Species 0.000 description 1
- 201000008808 Fibrosarcoma Diseases 0.000 description 1
- 229920001917 Ficoll Polymers 0.000 description 1
- 244000182067 Fraxinus ornus Species 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101000918983 Homo sapiens Neutrophil defensin 1 Proteins 0.000 description 1
- 101000766306 Homo sapiens Serotransferrin Proteins 0.000 description 1
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 1
- 101000818522 Homo sapiens fMet-Leu-Phe receptor Proteins 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- 108010016183 Human immunodeficiency virus 1 p16 protease Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 108010058683 Immobilized Proteins Proteins 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 102000004889 Interleukin-6 Human genes 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 102000008133 Iron-Binding Proteins Human genes 0.000 description 1
- 108010035210 Iron-Binding Proteins Proteins 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- 239000000232 Lipid Bilayer Substances 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 1
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000186366 Mycobacterium bovis Species 0.000 description 1
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 1
- 108010008211 N-Formylmethionine Leucyl-Phenylalanine Proteins 0.000 description 1
- 101800000287 Neutrophil defensin 2 Proteins 0.000 description 1
- 102400001060 Neutrophil defensin 2 Human genes 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 102000016387 Pancreatic elastase Human genes 0.000 description 1
- 108010067372 Pancreatic elastase Proteins 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 239000012979 RPMI medium Substances 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 241000607729 Salmonella enterica subsp. enterica serovar Abortus Species 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 229910052776 Thorium Inorganic materials 0.000 description 1
- 101710201242 Tracheal antimicrobial peptide Proteins 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 102100040247 Tumor necrosis factor Human genes 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001355 anti-mycobacterial effect Effects 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 108010009352 antilipopolysaccharide factor (Limulus) Proteins 0.000 description 1
- 238000002802 antimicrobial activity assay Methods 0.000 description 1
- 229960004405 aprotinin Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 239000012911 assay medium Substances 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 108091022598 bovine tracheal antimicrobial peptide Proteins 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 150000001720 carbohydrates Chemical group 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 108010033380 cathepsin-6 Proteins 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 230000004656 cell transport Effects 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 230000009920 chelation Effects 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- PRQROPMIIGLWRP-BZSNNMDCSA-N chemotactic peptide Chemical compound CSCC[C@H](NC=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 PRQROPMIIGLWRP-BZSNNMDCSA-N 0.000 description 1
- 229940080701 chymosin Drugs 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 1
- 230000001332 colony forming effect Effects 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 229960002086 dextran Drugs 0.000 description 1
- 229960000633 dextran sulfate Drugs 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000007598 dipping method Methods 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 230000001882 diuretic effect Effects 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 239000003221 ear drop Substances 0.000 description 1
- 229940047652 ear drops Drugs 0.000 description 1
- 230000000678 effect on lipid Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 102100021145 fMet-Leu-Phe receptor Human genes 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 238000010230 functional analysis Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 231100000234 hepatic damage Toxicity 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 230000009215 host defense mechanism Effects 0.000 description 1
- 102000018474 human neutrophil peptide 1 Human genes 0.000 description 1
- 235000003642 hunger Nutrition 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 210000005007 innate immune system Anatomy 0.000 description 1
- 229940100601 interleukin-6 Drugs 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 231100000225 lethality Toxicity 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000008818 liver damage Effects 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 210000003712 lysosome Anatomy 0.000 description 1
- 230000001868 lysosomic effect Effects 0.000 description 1
- 230000002101 lytic effect Effects 0.000 description 1
- VDXZNPDIRNWWCW-JFTDCZMZSA-N melittin Chemical compound NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(N)=O)CC1=CNC2=CC=CC=C12 VDXZNPDIRNWWCW-JFTDCZMZSA-N 0.000 description 1
- 230000034153 membrane organization Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 230000003641 microbiacidal effect Effects 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000002433 mononuclear leukocyte Anatomy 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- GNOLWGAJQVLBSM-UHFFFAOYSA-N n,n,5,7-tetramethyl-1,2,3,4-tetrahydronaphthalen-1-amine Chemical compound C1=C(C)C=C2C(N(C)C)CCCC2=C1C GNOLWGAJQVLBSM-UHFFFAOYSA-N 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000004134 neutrophil mediated immunity Effects 0.000 description 1
- GRZXCHIIZXMEPJ-HTLKCAKFSA-N neutrophil peptide-2 Chemical compound C([C@H]1C(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@H](C(N[C@@H](C)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=4C=CC(O)=CC=4)NC(=O)[C@@H](N)CSSC[C@H](NC2=O)C(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](C)C(=O)N3)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](C)C(=O)N1)[C@@H](C)CC)[C@@H](C)O)=O)[C@@H](C)CC)C1=CC=CC=C1 GRZXCHIIZXMEPJ-HTLKCAKFSA-N 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 231100001083 no cytotoxicity Toxicity 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 238000012261 overproduction Methods 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 229950000964 pepstatin Drugs 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 235000020030 perry Nutrition 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- WQVJHHACXVLGBL-GOVYWFKWSA-N polymyxin B1 Polymers N1C(=O)[C@H](CCN)NC(=O)[C@@H](NC(=O)[C@H](CCN)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCN)NC(=O)CCCC[C@H](C)CC)CCNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1CC1=CC=CC=C1 WQVJHHACXVLGBL-GOVYWFKWSA-N 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 108010005636 polypeptide C Proteins 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 230000004537 potential cytotoxicity Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 230000003161 proteinsynthetic effect Effects 0.000 description 1
- XNSAINXGIQZQOO-SRVKXCTJSA-N protirelin Chemical compound NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H]1NC(=O)CC1)CC1=CN=CN1 XNSAINXGIQZQOO-SRVKXCTJSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000003014 reinforcing effect Effects 0.000 description 1
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 238000009738 saturating Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000001235 sensitizing effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 238000009331 sowing Methods 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000037351 starvation Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 231100000057 systemic toxicity Toxicity 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- QHTGVJBNKLTDJN-ONHACJEVSA-N tracheal antimicrobial peptide Chemical compound N([C@H](C(=O)N[C@@H](CO)C(=O)N[C@@H]1C(=O)N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@H](C(N[C@H]2CSSC[C@H]3C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(N[C@@H](CSSC[C@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]4CCCN4C(=O)[C@H](C(C)C)NC2=O)C(=O)N2[C@@H](CCC2)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N3)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(O)=O)=O)CSSC1)C(C)C)C(C)C)=O)[C@@H](C)CC)C(C)C)C(C)C)C(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CC(N)=O QHTGVJBNKLTDJN-ONHACJEVSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 241001446247 uncultured actinomycete Species 0.000 description 1
- 238000012762 unpaired Student’s t-test Methods 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000013022 venting Methods 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 210000000707 wrist Anatomy 0.000 description 1
- KRJOFJHOZZPBKI-KSWODRSDSA-N α-defensin-1 Chemical compound C([C@H]1C(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@H](C(N[C@@H](C)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=4C=CC(O)=CC=4)NC(=O)[C@H](CSSC[C@H](NC2=O)C(O)=O)NC(=O)[C@H](C)N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](C)C(=O)N3)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](C)C(=O)N1)[C@@H](C)CC)[C@@H](C)O)=O)[C@@H](C)CC)C1=CC=CC=C1 KRJOFJHOZZPBKI-KSWODRSDSA-N 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/245,527 | 1999-02-05 | ||
| US09/245,527 US6399570B1 (en) | 1999-02-05 | 1999-02-05 | Antimicrobial/endotoxin neutralizing polypeptide |
| PCT/IB2000/000271 WO2000049040A2 (en) | 1999-02-05 | 2000-01-27 | Antimicrobial/endotoxin neutralizing polypeptide |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2002541066A JP2002541066A (ja) | 2002-12-03 |
| JP2002541066A5 true JP2002541066A5 (enExample) | 2007-03-08 |
Family
ID=22927039
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000599777A Pending JP2002541066A (ja) | 1999-02-05 | 2000-01-27 | 抗微生物薬／エンドトキシンを中和するポリペプチド |
Country Status (12)
| Country | Link |
|---|---|
| US (2) | US6399570B1 (enExample) |
| EP (1) | EP1151009B1 (enExample) |
| JP (1) | JP2002541066A (enExample) |
| CN (1) | CN1362969A (enExample) |
| AT (1) | ATE373679T1 (enExample) |
| AU (1) | AU758150B2 (enExample) |
| CA (1) | CA2362153C (enExample) |
| DE (1) | DE60036456T2 (enExample) |
| DK (1) | DK1151009T3 (enExample) |
| ES (1) | ES2293892T3 (enExample) |
| MX (1) | MXPA01007956A (enExample) |
| WO (1) | WO2000049040A2 (enExample) |
Families Citing this family (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL94183A (en) * | 1989-05-05 | 2003-09-17 | Baylor College Medicine | cDNA SEQUENCE CODING FOR HUMAN LACTOFERRIN PROTEIN OR PORTION THEREOF AND LACTOFERRIN PROTEIN PRODUCED FROM SAID SEQUENCE |
| US6399570B1 (en) | 1999-02-05 | 2002-06-04 | Agennix, Inc. | Antimicrobial/endotoxin neutralizing polypeptide |
| US7060677B1 (en) | 1999-11-11 | 2006-06-13 | Am-Pharma B.V. | Antimicrobial activity of the first cationic cluster of human lactoferrin |
| WO2003099323A1 (en) * | 2002-05-10 | 2003-12-04 | Agennix Incorporated | Lactoferrin in the treatment of malignant neoplasms and other hyperproliferative diseases |
| WO2003099207A2 (en) * | 2002-05-24 | 2003-12-04 | Agennix Incorporated | Oral lactoferrin in the treatment of respiratory disorders |
| EP1545587B1 (en) * | 2002-09-16 | 2011-02-09 | Agennix Incorporated | Lactoferrin compositions and methods of diabetic ulcer treatment |
| CA2508912A1 (en) * | 2002-12-06 | 2004-06-24 | Agennix Incorporated | Oral lactoferrin in the treatment of sepsis |
| AU2003296447A1 (en) * | 2002-12-10 | 2004-06-30 | Agennix Incorporated | Lactoferrin as an agent in the prevention of organ transplant rejection and graft-versus-host-disease |
| US7034126B2 (en) | 2003-05-14 | 2006-04-25 | Agennix, Inc. | Lactoferrin in the treatment of diabetes mellitus |
| US8105615B2 (en) * | 2003-06-06 | 2012-01-31 | Agennix Incorporated | Lactoferrin as an adjuvant in cancer vaccines |
| US20050075277A1 (en) * | 2003-07-10 | 2005-04-07 | Agennix Incorporated | Use of lactoferrin in prophylaxis against infection and/or inflammation in immunosuppressed subjects |
| US7125963B2 (en) * | 2004-03-03 | 2006-10-24 | En N Tech Inc | Treatments for contaminant reduction in lactoferrin preparations and lactoferrin containing compositions |
| WO2006047744A2 (en) * | 2004-10-26 | 2006-05-04 | Agennix Incorporated | Compositions of lactoferrin related peptides and uses thereof |
| CA2646833C (en) | 2005-12-30 | 2019-07-30 | Evonik Roehm Gmbh | Peptides useful as cell-penetrating peptides |
| EP2050461A1 (en) | 2007-10-19 | 2009-04-22 | PharmaSurgics in Sweden AB | Peptides based on the sequence of human lactoferrin and their use |
| EP2060586A1 (en) | 2007-11-14 | 2009-05-20 | PharmaSurgics in Sweden AB | New synthetic arginine substituted peptides and their use |
| US20090209488A1 (en) * | 2008-02-19 | 2009-08-20 | Roger Wayne Brown | Compositions for the treatment of exercise induced asthma |
| US20090208588A1 (en) * | 2008-02-19 | 2009-08-20 | Roger Wayne Brown | GERD carbohydrate compositions |
| US20090209489A1 (en) * | 2008-02-19 | 2009-08-20 | Roger Wayne Brown | Compositions for the treatment of diabetis, system PH disorders, high blood pressure, and a cancer marker system |
| US20090209486A1 (en) * | 2008-02-19 | 2009-08-20 | Roger Wayne Brown | Compositions of carbohydrates as dietary supplements |
| US20090209487A1 (en) * | 2008-02-19 | 2009-08-20 | Roger Wayne Brown | Compositions of carbohydrates as dietary supplements |
| CN101294188B (zh) * | 2008-06-20 | 2011-06-15 | 江南大学 | 乳铁蛋白抗菌肽及其制备方法与它们的用途 |
| JP5177901B2 (ja) * | 2009-12-02 | 2013-04-10 | 株式会社明治 | 栄養組成物 |
| CN101798337B (zh) * | 2010-01-29 | 2013-04-24 | 中国人民解放军第三军医大学第一附属医院 | 内毒素中和肽突变体及其应用 |
| EP2481751A1 (en) | 2011-01-26 | 2012-08-01 | PharmaSurgics in Sweden AB | Human lactoferrin derived peptides |
| JP5763024B2 (ja) * | 2012-09-07 | 2015-08-12 | 株式会社明治 | 栄養組成物 |
| CN105101796B (zh) * | 2013-02-06 | 2017-06-06 | 中央研究院 | 衍生自b型肝炎病毒核蛋白精氨酸密集区的抗菌胜肽 |
| WO2016056665A1 (ja) * | 2014-10-08 | 2016-04-14 | 学校法人慶應義塾 | 白血球の細胞外トラップ形成の阻害剤 |
| US10308679B2 (en) | 2014-11-03 | 2019-06-04 | Merck Patent Gmbh | Soluble intein fusion proteins and methods for purifying biomolecules |
| JP7161263B6 (ja) * | 2016-05-27 | 2023-03-20 | アカデミア シニカ | アルギニンリッチドメインに由来する改変抗微生物ペプチド |
| CN105999236A (zh) * | 2016-07-06 | 2016-10-12 | 方雅悯 | 一种治疗牛乳房炎的药剂及其应用 |
Family Cites Families (64)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4977137B1 (en) | 1987-06-03 | 1994-06-28 | Baylor College Medicine | Lactoferrin as a dietary ingredient promoting the growth of the gastrointestinal tract |
| US6020015A (en) * | 1988-09-22 | 2000-02-01 | Gaull; Gerald E. | Infant formula compositions and nutrition containing genetically engineered human milk proteins |
| JP2805490B2 (ja) * | 1989-02-07 | 1998-09-30 | 雪印乳業株式会社 | 細菌毒素中和剤 |
| US5141743A (en) * | 1989-04-27 | 1992-08-25 | University Technologies International, Inc. | Method for isolating and purifying transferrin and lactoferrin receptor proteins and vaccines containing the same |
| US5571697A (en) * | 1989-05-05 | 1996-11-05 | Baylor College Of Medicine Texas Medical Center | Expression of processed recombinant lactoferrin and lactoferrin polypeptide fragments from a fusion product in Aspergillus |
| US6100054A (en) | 1989-05-05 | 2000-08-08 | Baylor College Of Medicine | Production for recombinant lactoferrin and lactoferrin polypeptides using DNA sequences in various organisms |
| US5849881A (en) * | 1989-05-05 | 1998-12-15 | Baylor College Medicine | Production of recombinant lactoferrin and lactoferrin polypeptides using cDNA sequences in various organisms |
| US5766939A (en) | 1989-05-05 | 1998-06-16 | Baylor College Of Medicine | Production of recombinant lactoferrin and lactoferrin polypeptides using CDNA sequences in various organisms |
| US5571691A (en) * | 1989-05-05 | 1996-11-05 | Baylor College Of Medicine | Production of recombinant lactoferrin and lactoferrin polypeptides using CDNA sequences in various organisms |
| IL94183A (en) * | 1989-05-05 | 2003-09-17 | Baylor College Medicine | cDNA SEQUENCE CODING FOR HUMAN LACTOFERRIN PROTEIN OR PORTION THEREOF AND LACTOFERRIN PROTEIN PRODUCED FROM SAID SEQUENCE |
| US5198419A (en) * | 1989-12-08 | 1993-03-30 | Immuno Japan Inc. | Formulated medicines for enhancing the efficacy of beta-lactam antibiotics in prophylaxis and treatment against infectious disease due to pathogenic bacteria |
| EP0438750B1 (en) | 1990-01-23 | 1993-10-27 | Morinaga Milk Industry Co., Ltd. | Lactoferrin hydrolyzate for use as an antibacterial agent |
| US6066469A (en) * | 1990-03-08 | 2000-05-23 | Ferro Dynamics, Inc. | Cloning, expression, and uses of human lactoferrin |
| US5240909B1 (en) * | 1990-03-14 | 1998-01-20 | Dietrich Nitsche | Use of lactoferrin for treatment of toxic effects of endotoxins |
| DE4008033A1 (de) | 1990-03-14 | 1991-09-19 | Nitsche Dietrich | Verwendung von lactoferrin zur bekaempfung der toxischen wirkung des endotoxins |
| JP2818056B2 (ja) | 1990-09-07 | 1998-10-30 | 森永乳業株式会社 | 抗菌性ペプチドおよび抗菌剤 |
| DE69124627T2 (de) * | 1990-11-13 | 1997-06-12 | Bio Serae Lab | Therapeutische agens bei hornhautverletzungen |
| JP3110078B2 (ja) | 1991-06-21 | 2000-11-20 | 森永乳業株式会社 | 高純度抗菌性ペプチドの大量製造法 |
| EP0629347B1 (en) | 1992-01-23 | 1997-07-02 | Morinaga Milk Industry Co., Ltd. | Antibacterial agent and treatment of article therewith |
| DE69322896T2 (de) * | 1992-03-02 | 1999-05-27 | Immuno Japan Inc., Tokio/Tokyo | Verwendung von Proteinen der Transferrin/Lactoferrin-Familie zur Stimulation des Immunsystems |
| ZA932568B (en) | 1992-04-24 | 1993-11-12 | Baylor College Midecine A Non | Production of recombinant human lactoferrin |
| JP3100005B2 (ja) * | 1992-07-28 | 2000-10-16 | 雪印乳業株式会社 | ヒト免疫不全ウィルス感染・増殖抑制剤 |
| US5733872A (en) | 1993-03-12 | 1998-03-31 | Xoma Corporation | Biologically active peptides from functional domains of bactericidal/permeability-increasing protein and uses thereof |
| JP3770624B2 (ja) | 1993-09-02 | 2006-04-26 | 雪印乳業株式会社 | ウィルス感染・増殖抑制剤 |
| WO1995022258A2 (en) * | 1994-02-16 | 1995-08-24 | Pharming Bv | Isolation of lactoferrin from milk |
| NL1000332C1 (nl) | 1994-08-31 | 1996-03-04 | Victor Smit | Graduele chemische modificatie van biologisch actieve peptiden en eiwitten. |
| JP3506274B2 (ja) | 1994-09-01 | 2004-03-15 | 雪印乳業株式会社 | 新規ペプチドおよび免疫賦活剤 |
| US5531989A (en) * | 1994-10-28 | 1996-07-02 | Metagenics, Inc. | Immunoglobulin and fiber-containing composition for human gastrointestinal health |
| JPH08165248A (ja) | 1994-12-15 | 1996-06-25 | Nobuo Kuriiwa | エンドトキシンによる炎症の抑止剤 |
| US5712247A (en) * | 1995-02-21 | 1998-01-27 | University Of North Carolina | Use of lactoferrin to modulate and/or neutralize heparin activity |
| JPH11504316A (ja) * | 1995-04-05 | 1999-04-20 | ザ ピコワー インスティテュート フォア メディカル リサーチ | 進行性グリコシル化終末産物に結合する薬剤及びその使用方法 |
| US20020016289A1 (en) * | 1995-06-01 | 2002-02-07 | Orla M. Conneely | Methods for treatment and prevention of helicobacter pylori infection using lactoferrin |
| US5834424A (en) * | 1995-07-12 | 1998-11-10 | Gambit International Limited | Use of lactoferrin for therapy of acute of chronic infectious diseases by the intracellular gram-positive pathogens streptococcus pyogenes and staphylococcus aureus |
| JP3878683B2 (ja) * | 1995-10-30 | 2007-02-07 | 森永乳業株式会社 | 抗菌性ペプチド組成物とその製造法 |
| JPH09165342A (ja) * | 1995-12-14 | 1997-06-24 | Morinaga Milk Ind Co Ltd | 抗真菌剤 |
| SE506529C2 (sv) * | 1996-01-23 | 1997-12-22 | Semper Ab | Användning av ett laktoperoxidassystem för framställning av ett läkemedel mot Helicobacter pylori |
| US6111081A (en) * | 1996-05-31 | 2000-08-29 | Baylor College Of Medicine | Lactoferrin variants and uses thereof |
| PL331563A1 (en) * | 1996-08-14 | 1999-07-19 | Novartis Ag | Peptide exhibiting activity being inhibitive in respect to pathogenic plants-attacking fungi v |
| US6503881B2 (en) * | 1996-08-21 | 2003-01-07 | Micrologix Biotech Inc. | Compositions and methods for treating infections using cationic peptides alone or in combination with antibiotics |
| JPH10182479A (ja) * | 1996-12-24 | 1998-07-07 | Morinaga Milk Ind Co Ltd | ペプチド誘導体類からなる薬剤 |
| AU6307698A (en) * | 1997-02-03 | 1998-08-25 | Pharming Bv | Useful properties of human lactoferrin and variants thereof |
| WO1998044940A1 (en) * | 1997-04-10 | 1998-10-15 | Agennix, Inc. | Use of lactoferin in the treatment of allergen induced disorders |
| FR2762850B1 (fr) * | 1997-05-02 | 2000-02-11 | Biocem | Lactoferrines recombinantes, leurs procedes de production par les plantes ainsi que leurs utilisations |
| US6849593B1 (en) | 1997-09-16 | 2005-02-01 | Pharis Biotec Gmbh | Bifidogenic peptides |
| US20020165128A1 (en) * | 1998-04-13 | 2002-11-07 | Plaut Andrew G. | Compositions and methods for proteolytically inactivating infectious agents using lactoferrin and related molecules |
| WO1999056732A1 (fr) * | 1998-04-30 | 1999-11-11 | Morinaga Milk Industry Co., Ltd. | Comprimes drageifies |
| US6258383B1 (en) * | 1998-08-14 | 2001-07-10 | Lactoferrin Products Company | Dietary supplement combining colostrum and lactoferrin in a mucosal delivery format |
| GB9818938D0 (en) * | 1998-08-28 | 1998-10-21 | Alpharma As | Bioactive peptides |
| US6719973B1 (en) * | 1998-12-24 | 2004-04-13 | National University Of Singapore | Recombinant proteins and peptides for endotoxin biosensors, endotoxin removal, and anti-microbial and anti-endotoxin therapeutics |
| US6399570B1 (en) | 1999-02-05 | 2002-06-04 | Agennix, Inc. | Antimicrobial/endotoxin neutralizing polypeptide |
| US6613741B2 (en) * | 1999-10-29 | 2003-09-02 | Ferro Dynamics, Inc. | Method for treating aseptic SIRS in humans and other animals |
| TWI237695B (en) * | 1999-12-14 | 2005-08-11 | Joy Biomedical Corp | Helicobacter pylori antigens in blood |
| US20040157277A1 (en) * | 2002-03-08 | 2004-08-12 | Clancy Robert Llewellyn | Methods for predicting and/or diagnosing the risk of gastric cancer |
| RU2165769C1 (ru) | 2000-07-13 | 2001-04-27 | Якубовская Раиса Ивановна | Антибактериальный, антиоксидантный, иммуномодулирующий и антиканцерогенный препарат и способ его применения |
| US7020715B2 (en) * | 2000-08-22 | 2006-03-28 | Adaptec, Inc. | Protocol stack for linking storage area networks over an existing LAN, MAN, or WAN |
| KR100454595B1 (ko) * | 2001-11-30 | 2004-10-28 | 주식회사 이지바이오 시스템 | 락토페리신 유전자 및 이를 도입한 형질전환 대장균 |
| WO2003099323A1 (en) * | 2002-05-10 | 2003-12-04 | Agennix Incorporated | Lactoferrin in the treatment of malignant neoplasms and other hyperproliferative diseases |
| WO2003099207A2 (en) * | 2002-05-24 | 2003-12-04 | Agennix Incorporated | Oral lactoferrin in the treatment of respiratory disorders |
| SE526038C2 (sv) * | 2002-07-08 | 2005-06-21 | Gambro Lundia Ab | Polymeraffinitetsmatris, förfarande för framställning därav och anvädning därav |
| EP1545587B1 (en) * | 2002-09-16 | 2011-02-09 | Agennix Incorporated | Lactoferrin compositions and methods of diabetic ulcer treatment |
| CA2508912A1 (en) * | 2002-12-06 | 2004-06-24 | Agennix Incorporated | Oral lactoferrin in the treatment of sepsis |
| CA2530454A1 (en) * | 2003-06-24 | 2005-01-13 | Akzo Nobel N.V. | Removal of lipopolysaccharides from protein- lipopolysaccharide complex es by nonflammable solvents |
| US20050075277A1 (en) * | 2003-07-10 | 2005-04-07 | Agennix Incorporated | Use of lactoferrin in prophylaxis against infection and/or inflammation in immunosuppressed subjects |
| WO2006047744A2 (en) * | 2004-10-26 | 2006-05-04 | Agennix Incorporated | Compositions of lactoferrin related peptides and uses thereof |
-
1999
- 1999-02-05 US US09/245,527 patent/US6399570B1/en not_active Expired - Fee Related
-
2000
- 2000-01-27 JP JP2000599777A patent/JP2002541066A/ja active Pending
- 2000-01-27 MX MXPA01007956A patent/MXPA01007956A/es not_active IP Right Cessation
- 2000-01-27 ES ES00906569T patent/ES2293892T3/es not_active Expired - Lifetime
- 2000-01-27 DE DE60036456T patent/DE60036456T2/de not_active Expired - Lifetime
- 2000-01-27 CN CN00804843A patent/CN1362969A/zh active Pending
- 2000-01-27 DK DK00906569T patent/DK1151009T3/da active
- 2000-01-27 CA CA002362153A patent/CA2362153C/en not_active Expired - Fee Related
- 2000-01-27 AU AU28226/00A patent/AU758150B2/en not_active Ceased
- 2000-01-27 AT AT00906569T patent/ATE373679T1/de not_active IP Right Cessation
- 2000-01-27 WO PCT/IB2000/000271 patent/WO2000049040A2/en not_active Ceased
- 2000-01-27 EP EP00906569A patent/EP1151009B1/en not_active Expired - Lifetime
-
2002
- 2002-05-13 US US10/145,651 patent/US7244706B2/en not_active Expired - Fee Related
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7244706B2 (en) | Antimicrobial/endotoxin neutralizing polypeptide | |
| JP2002541066A5 (enExample) | ||
| US20240018192A1 (en) | Lysin-antimicrobial peptide (amp) polypeptide constructs, lysins, isolated polynucleotides encoding same and uses thereof | |
| Abdolhosseini et al. | Lysine substitutions convert a bacterial-agglutinating peptide into a bactericidal peptide that retains anti-lipopolysaccharide activity and low hemolytic activity | |
| US20210147498A1 (en) | Use of gram-negative lysin-antimicrobial peptide (amp) polypeptide constructs in pulmonary surfactant and biofilms | |
| US20220402984A1 (en) | Lysin-antimicrobial peptide (amp) polypeptide constructs, lysins, isolated polynucleotides encoding same and uses thereof | |
| Mak et al. | The increased bactericidal activity of a fatty acid-modified synthetic antimicrobial peptide of human cathepsin G correlates with its enhanced capacity to interact with model membranes | |
| CA2076529A1 (en) | Compositions and methods for treating infections caused by organisms sensitive to beta-lactam antibiotics | |
| Shafer et al. | Tailoring an antibacterial peptide of human lysosomal cathepsin G to enhance its broad-spectrum action against antibiotic-resistant bacterial pathogens | |
| CA3096236A1 (en) | Antimicrobial, bacteriophage-derived polypeptides and their use against gram-negative bacteria | |
| US20210324359A1 (en) | Use of gram-negative lysin-antimicrobial peptide (amp) polypeptide constructs in treating endocarditis | |
| PerumalSamy et al. | Snake venom proteins: development into antimicrobial and wound healing agents | |
| US20220411473A1 (en) | Lysin-antimicrobial peptide (amp) polypeptide constructs, lysins, isolated polynucleotides encoding same and uses thereof | |
| JP2022526978A (ja) | ヒト血清の存在下でシュードモナス・エルギノーサに対する殺菌活性を有する溶解素及びその誘導体 | |
| US12384821B2 (en) | Antimicrobial peptides and compositions, methods, articles and kits relating thereto | |
| CA3095473A1 (en) | Lysin-antimicrobial peptide (amp) polypeptide constructs, lysins, isolated polynucleotides encoding same and uses thereof | |
| WO2024256710A2 (en) | Engineered lysin polypeptide constructs active against gram-negative bacteria |