CA2665186A1 - Stabilized therapeutic small helical antiviral peptides - Google Patents
Stabilized therapeutic small helical antiviral peptides Download PDFInfo
- Publication number
- CA2665186A1 CA2665186A1 CA002665186A CA2665186A CA2665186A1 CA 2665186 A1 CA2665186 A1 CA 2665186A1 CA 002665186 A CA002665186 A CA 002665186A CA 2665186 A CA2665186 A CA 2665186A CA 2665186 A1 CA2665186 A1 CA 2665186A1
- Authority
- CA
- Canada
- Prior art keywords
- peptide
- amino acids
- capsid
- mammal
- containing virus
- 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.)
- Abandoned
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 173
- 230000000840 anti-viral effect Effects 0.000 title claims description 19
- 230000001225 therapeutic effect Effects 0.000 title claims description 19
- 102000004196 processed proteins & peptides Human genes 0.000 title abstract description 59
- 241000700605 Viruses Species 0.000 claims abstract description 83
- 238000000034 method Methods 0.000 claims abstract description 78
- 210000000234 capsid Anatomy 0.000 claims abstract description 75
- 241000124008 Mammalia Species 0.000 claims abstract description 48
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 18
- 208000015181 infectious disease Diseases 0.000 claims abstract description 14
- 230000010076 replication Effects 0.000 claims abstract description 13
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 8
- 150000001413 amino acids Chemical class 0.000 claims description 105
- 150000001875 compounds Chemical class 0.000 claims description 27
- 238000011282 treatment Methods 0.000 claims description 25
- 239000000427 antigen Substances 0.000 claims description 18
- 108091007433 antigens Proteins 0.000 claims description 18
- 102000036639 antigens Human genes 0.000 claims description 18
- 239000003814 drug Substances 0.000 claims description 12
- 229910052799 carbon Inorganic materials 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 241001430294 unidentified retrovirus Species 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 241000713666 Lentivirus Species 0.000 claims description 8
- 125000000304 alkynyl group Chemical group 0.000 claims description 7
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 238000005865 alkene metathesis reaction Methods 0.000 claims description 5
- 230000008878 coupling Effects 0.000 claims description 5
- 238000010168 coupling process Methods 0.000 claims description 5
- 238000005859 coupling reaction Methods 0.000 claims description 5
- 230000001413 cellular effect Effects 0.000 claims description 4
- 210000003754 fetus Anatomy 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 101100533890 Hypocrea jecorina (strain QM6a) sor3 gene Proteins 0.000 claims description 3
- 101100533874 Hypocrea jecorina (strain QM6a) sor5 gene Proteins 0.000 claims description 3
- 102000015636 Oligopeptides Human genes 0.000 claims description 3
- 108010038807 Oligopeptides Proteins 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000001475 halogen functional group Chemical group 0.000 claims description 3
- 238000005304 joining Methods 0.000 claims description 3
- 150000002894 organic compounds Chemical class 0.000 claims description 3
- 238000010532 solid phase synthesis reaction Methods 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- 229940124597 therapeutic agent Drugs 0.000 claims description 3
- 108090000371 Esterases Proteins 0.000 claims description 2
- 230000002285 radioactive effect Effects 0.000 claims description 2
- 210000004027 cell Anatomy 0.000 description 102
- 229940024606 amino acid Drugs 0.000 description 70
- 235000001014 amino acid Nutrition 0.000 description 69
- 239000002245 particle Substances 0.000 description 30
- 108090000623 proteins and genes Proteins 0.000 description 25
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 24
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 24
- 235000018102 proteins Nutrition 0.000 description 24
- 102000004169 proteins and genes Human genes 0.000 description 24
- 241000725303 Human immunodeficiency virus Species 0.000 description 16
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 16
- 230000005764 inhibitory process Effects 0.000 description 16
- 238000005481 NMR spectroscopy Methods 0.000 description 15
- 238000000338 in vitro Methods 0.000 description 14
- 239000000203 mixture Substances 0.000 description 12
- 239000000872 buffer Substances 0.000 description 11
- 238000001727 in vivo Methods 0.000 description 10
- 239000003112 inhibitor Substances 0.000 description 10
- -1 small molecule compounds Chemical class 0.000 description 10
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 230000003612 virological effect Effects 0.000 description 9
- 101710177291 Gag polyprotein Proteins 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- 108010027225 gag-pol Fusion Proteins Proteins 0.000 description 8
- 238000001890 transfection Methods 0.000 description 8
- 210000004899 c-terminal region Anatomy 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 101710205625 Capsid protein p24 Proteins 0.000 description 6
- 239000004215 Carbon black (E152) Substances 0.000 description 6
- 101710177166 Phosphoprotein Proteins 0.000 description 6
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 6
- 101710149279 Small delta antigen Proteins 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 231100000135 cytotoxicity Toxicity 0.000 description 6
- 230000003013 cytotoxicity Effects 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 238000006467 substitution reaction Methods 0.000 description 6
- 238000002965 ELISA Methods 0.000 description 5
- 101710170658 Endogenous retrovirus group K member 10 Gag polyprotein Proteins 0.000 description 5
- 101710186314 Endogenous retrovirus group K member 21 Gag polyprotein Proteins 0.000 description 5
- 101710162093 Endogenous retrovirus group K member 24 Gag polyprotein Proteins 0.000 description 5
- 101710094596 Endogenous retrovirus group K member 8 Gag polyprotein Proteins 0.000 description 5
- 101710177443 Endogenous retrovirus group K member 9 Gag polyprotein Proteins 0.000 description 5
- 101710203526 Integrase Proteins 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 230000008045 co-localization Effects 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 238000011534 incubation Methods 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- 210000002487 multivesicular body Anatomy 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 108090000565 Capsid Proteins Proteins 0.000 description 4
- 102100023321 Ceruloplasmin Human genes 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 210000000170 cell membrane Anatomy 0.000 description 4
- 238000001142 circular dichroism spectrum Methods 0.000 description 4
- 238000001493 electron microscopy Methods 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 235000011187 glycerol Nutrition 0.000 description 4
- 229930195733 hydrocarbon Natural products 0.000 description 4
- 238000013507 mapping Methods 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 230000002503 metabolic effect Effects 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 239000000816 peptidomimetic Substances 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 239000000829 suppository Substances 0.000 description 4
- 238000004448 titration Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical class CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 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
- 101710125418 Major capsid protein Proteins 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000012980 RPMI-1640 medium Substances 0.000 description 3
- 235000004279 alanine Nutrition 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 238000000502 dialysis Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000012091 fetal bovine serum Substances 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 150000002430 hydrocarbons Chemical class 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 230000002209 hydrophobic effect Effects 0.000 description 3
- 230000035699 permeability Effects 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 2
- WEYNBWVKOYCCQT-UHFFFAOYSA-N 1-(3-chloro-4-methylphenyl)-3-{2-[({5-[(dimethylamino)methyl]-2-furyl}methyl)thio]ethyl}urea Chemical compound O1C(CN(C)C)=CC=C1CSCCNC(=O)NC1=CC=C(C)C(Cl)=C1 WEYNBWVKOYCCQT-UHFFFAOYSA-N 0.000 description 2
- 102100027241 Adenylyl cyclase-associated protein 1 Human genes 0.000 description 2
- 101710137115 Adenylyl cyclase-associated protein 1 Proteins 0.000 description 2
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 108010079882 Bax protein (53-86) Proteins 0.000 description 2
- 241000711573 Coronaviridae Species 0.000 description 2
- 241000709661 Enterovirus Species 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 208000031886 HIV Infections Diseases 0.000 description 2
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- 108090001074 Nucleocapsid Proteins Proteins 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- COQLPRJCUIATTQ-UHFFFAOYSA-N Uranyl acetate Chemical compound O.O.O=[U]=O.CC(O)=O.CC(O)=O COQLPRJCUIATTQ-UHFFFAOYSA-N 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 239000012062 aqueous buffer Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 238000000423 cell based assay Methods 0.000 description 2
- 230000034303 cell budding Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000002983 circular dichroism Methods 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 238000004624 confocal microscopy Methods 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 238000000635 electron micrograph Methods 0.000 description 2
- 238000010218 electron microscopic analysis Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 238000000990 heteronuclear single quantum coherence spectrum Methods 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 125000001165 hydrophobic group Chemical group 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 230000002458 infectious effect Effects 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 230000035800 maturation Effects 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000012679 serum free medium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- IHQKEDIOMGYHEB-UHFFFAOYSA-M sodium dimethylarsinate Chemical compound [Na+].C[As](C)([O-])=O IHQKEDIOMGYHEB-UHFFFAOYSA-M 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 230000000087 stabilizing effect Effects 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 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 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 210000004291 uterus Anatomy 0.000 description 2
- 239000004474 valine Substances 0.000 description 2
- 235000014393 valine Nutrition 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 1
- FUOOLUPWFVMBKG-UHFFFAOYSA-N 2-Aminoisobutyric acid Chemical compound CC(C)(N)C(O)=O FUOOLUPWFVMBKG-UHFFFAOYSA-N 0.000 description 1
- 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 1
- QGJZLNKBHJESQX-UHFFFAOYSA-N 3-Epi-Betulin-Saeure Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C(O)=O)CCC(C(=C)C)C5C4CCC3C21C QGJZLNKBHJESQX-UHFFFAOYSA-N 0.000 description 1
- CLOUCVRNYSHRCF-UHFFFAOYSA-N 3beta-Hydroxy-20(29)-Lupen-3,27-oic acid Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C(O)=O)CCC5(C)CCC(C(=C)C)C5C4CCC3C21C CLOUCVRNYSHRCF-UHFFFAOYSA-N 0.000 description 1
- KAUQJMHLAFIZDU-UHFFFAOYSA-N 6-Hydroxy-2-naphthoic acid Chemical compound C1=C(O)C=CC2=CC(C(=O)O)=CC=C21 KAUQJMHLAFIZDU-UHFFFAOYSA-N 0.000 description 1
- JDDWRLPTKIOUOF-UHFFFAOYSA-N 9h-fluoren-9-ylmethyl n-[[4-[2-[bis(4-methylphenyl)methylamino]-2-oxoethoxy]phenyl]-(2,4-dimethoxyphenyl)methyl]carbamate Chemical compound COC1=CC(OC)=CC=C1C(C=1C=CC(OCC(=O)NC(C=2C=CC(C)=CC=2)C=2C=CC(C)=CC=2)=CC=1)NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21 JDDWRLPTKIOUOF-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 102100021879 Adenylyl cyclase-associated protein 2 Human genes 0.000 description 1
- 101710137132 Adenylyl cyclase-associated protein 2 Proteins 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 241000203069 Archaea Species 0.000 description 1
- 241000712891 Arenavirus Species 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 102100026596 Bcl-2-like protein 1 Human genes 0.000 description 1
- DIZWSDNSTNAYHK-XGWVBXMLSA-N Betulinic acid Natural products CC(=C)[C@@H]1C[C@H]([C@H]2CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC[C@H](O)C(C)(C)[C@@H]5CC[C@@]34C)[C@@H]12)C(=O)O DIZWSDNSTNAYHK-XGWVBXMLSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 241000713704 Bovine immunodeficiency virus Species 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 102000020313 Cell-Penetrating Peptides Human genes 0.000 description 1
- 108010051109 Cell-Penetrating Peptides Proteins 0.000 description 1
- 108010038447 Chromogranin A Proteins 0.000 description 1
- 102100031186 Chromogranin-A Human genes 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- 150000008574 D-amino acids Chemical class 0.000 description 1
- GZCGUPFRVQAUEE-AEKYUDOOSA-N D-glucose-(13)C6 Chemical compound O[13CH2][13C@@H](O)[13C@@H](O)[13C@H](O)[13C@@H](O)[13CH]=O GZCGUPFRVQAUEE-AEKYUDOOSA-N 0.000 description 1
- 208000001490 Dengue Diseases 0.000 description 1
- 206010012310 Dengue fever Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 201000011001 Ebola Hemorrhagic Fever Diseases 0.000 description 1
- 241001115402 Ebolavirus Species 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 241000991587 Enterovirus C Species 0.000 description 1
- 241001198387 Escherichia coli BL21(DE3) Species 0.000 description 1
- 241000713800 Feline immunodeficiency virus Species 0.000 description 1
- 241000282324 Felis Species 0.000 description 1
- 241000711950 Filoviridae Species 0.000 description 1
- 241000710781 Flaviviridae Species 0.000 description 1
- 241000710831 Flavivirus Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 238000001535 HNCA Methods 0.000 description 1
- 238000001321 HNCO Methods 0.000 description 1
- 238000002130 HNCOCA Methods 0.000 description 1
- 241000711549 Hepacivirus C Species 0.000 description 1
- 241000700721 Hepatitis B virus Species 0.000 description 1
- 241000709721 Hepatovirus A Species 0.000 description 1
- 241000700586 Herpesviridae Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000579613 Homo sapiens U6 snRNA-associated Sm-like protein LSm5 Proteins 0.000 description 1
- 206010020460 Human T-cell lymphotropic virus type I infection Diseases 0.000 description 1
- 241000714260 Human T-lymphotropic virus 1 Species 0.000 description 1
- 241000714259 Human T-lymphotropic virus 2 Species 0.000 description 1
- 241000713340 Human immunodeficiency virus 2 Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- OWIKHYCFFJSOEH-UHFFFAOYSA-N Isocyanic acid Chemical compound N=C=O OWIKHYCFFJSOEH-UHFFFAOYSA-N 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 241001115401 Marburgvirus Species 0.000 description 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 1
- BKAYIFDRRZZKNF-VIFPVBQESA-N N-acetylcarnosine Chemical compound CC(=O)NCCC(=O)N[C@H](C(O)=O)CC1=CN=CN1 BKAYIFDRRZZKNF-VIFPVBQESA-N 0.000 description 1
- 241000150452 Orthohantavirus Species 0.000 description 1
- 241000712464 Orthomyxoviridae Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241000711504 Paramyxoviridae Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- 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 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 241000150350 Peribunyaviridae Species 0.000 description 1
- 241000223960 Plasmodium falciparum Species 0.000 description 1
- 108010090931 Proto-Oncogene Proteins c-bcl-2 Proteins 0.000 description 1
- 102000013535 Proto-Oncogene Proteins c-bcl-2 Human genes 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 241000712907 Retroviridae Species 0.000 description 1
- 241000710799 Rubella virus Species 0.000 description 1
- 241000315672 SARS coronavirus Species 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 241000713311 Simian immunodeficiency virus Species 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 208000004006 Tick-borne encephalitis Diseases 0.000 description 1
- 241000710924 Togaviridae Species 0.000 description 1
- 241000711517 Torovirus Species 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 102100028261 U6 snRNA-associated Sm-like protein LSm5 Human genes 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 208000003152 Yellow Fever Diseases 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- QGJZLNKBHJESQX-FZFNOLFKSA-N betulinic acid Chemical compound C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CC[C@@H](C(=C)C)[C@@H]5[C@H]4CC[C@@H]3[C@]21C QGJZLNKBHJESQX-FZFNOLFKSA-N 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- HOQPTLCRWVZIQZ-UHFFFAOYSA-H bis[[2-(5-hydroxy-4,7-dioxo-1,3,2$l^{2}-dioxaplumbepan-5-yl)acetyl]oxy]lead Chemical compound [Pb+2].[Pb+2].[Pb+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HOQPTLCRWVZIQZ-UHFFFAOYSA-H 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- HRHJHXJQMNWQTF-UHFFFAOYSA-N cannabichromenic acid Chemical compound O1C(C)(CCC=C(C)C)C=CC2=C1C=C(CCCCC)C(C(O)=O)=C2O HRHJHXJQMNWQTF-UHFFFAOYSA-N 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 210000004671 cell-free system Anatomy 0.000 description 1
- 230000004700 cellular uptake Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000000942 confocal micrograph Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229940099112 cornstarch Drugs 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000012228 culture supernatant Substances 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
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 125000001295 dansyl group Chemical group [H]C1=C([H])C(N(C([H])([H])[H])C([H])([H])[H])=C2C([H])=C([H])C([H])=C(C2=C1[H])S(*)(=O)=O 0.000 description 1
- 208000025729 dengue disease Diseases 0.000 description 1
- 238000000326 densiometry Methods 0.000 description 1
- 238000000432 density-gradient centrifugation Methods 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- PZXJOHSZQAEJFE-UHFFFAOYSA-N dihydrobetulinic acid Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C(O)=O)CCC(C(C)C)C5C4CCC3C21C PZXJOHSZQAEJFE-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 235000019800 disodium phosphate Nutrition 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 210000001163 endosome Anatomy 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940079360 enema for constipation Drugs 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000006882 induction of apoptosis Effects 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 230000001524 infective effect Effects 0.000 description 1
- 238000013383 initial experiment Methods 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000010189 intracellular transport Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 150000003951 lactams Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 235000018977 lysine Nutrition 0.000 description 1
- 150000002669 lysines Chemical class 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960001047 methyl salicylate Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- CPTIBDHUFVHUJK-NZYDNVMFSA-N mitopodozide Chemical compound C1([C@@H]2C3=CC=4OCOC=4C=C3[C@H](O)[C@@H](CO)[C@@H]2C(=O)NNCC)=CC(OC)=C(OC)C(OC)=C1 CPTIBDHUFVHUJK-NZYDNVMFSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
- MQYXUWHLBZFQQO-UHFFFAOYSA-N nepehinol Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C)CCC(C(=C)C)C5C4CCC3C21C MQYXUWHLBZFQQO-UHFFFAOYSA-N 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229960002715 nicotine Drugs 0.000 description 1
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
- 125000006502 nitrobenzyl group Chemical group 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- 238000000033 nuclear magnetic resonance titration Methods 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 229940114930 potassium stearate Drugs 0.000 description 1
- ANBFRLKBEIFNQU-UHFFFAOYSA-M potassium;octadecanoate Chemical compound [K+].CCCCCCCCCCCCCCCCCC([O-])=O ANBFRLKBEIFNQU-UHFFFAOYSA-M 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000000861 pro-apoptotic effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 210000000664 rectum Anatomy 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
- 230000033458 reproduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- QEKVQYCTJHJBOF-UHFFFAOYSA-L ruthenium(2+);styrene;triphenylphosphane;dichloride Chemical compound Cl[Ru]Cl.C=CC1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QEKVQYCTJHJBOF-UHFFFAOYSA-L 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 235000004400 serine Nutrition 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 235000008521 threonine Nutrition 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Virology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Tropical Medicine & Parasitology (AREA)
- AIDS & HIV (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US84955106P | 2006-10-05 | 2006-10-05 | |
| US60/849,551 | 2006-10-05 | ||
| PCT/US2007/021156 WO2008045238A2 (en) | 2006-10-05 | 2007-10-02 | Stabilized therapeutic small helical antiviral peptides |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2665186A1 true CA2665186A1 (en) | 2008-04-17 |
Family
ID=39283347
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002665186A Abandoned CA2665186A1 (en) | 2006-10-05 | 2007-10-02 | Stabilized therapeutic small helical antiviral peptides |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US8940864B2 (enExample) |
| EP (2) | EP2073829B1 (enExample) |
| JP (1) | JP2010505831A (enExample) |
| AU (1) | AU2007307254A1 (enExample) |
| CA (1) | CA2665186A1 (enExample) |
| ES (1) | ES2387827T3 (enExample) |
| WO (1) | WO2008045238A2 (enExample) |
| ZA (1) | ZA200901248B (enExample) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8937154B2 (en) * | 2006-10-05 | 2015-01-20 | New York Blood Center, Inc. | Stabilized therapeutic small helical antiviral peptides |
| EP2118123B1 (en) | 2007-01-31 | 2015-10-14 | Dana-Farber Cancer Institute, Inc. | Stabilized p53 peptides and uses thereof |
| EP3159352B1 (en) | 2007-03-28 | 2023-08-02 | President and Fellows of Harvard College | Stitched polypeptides |
| JP2011522796A (ja) * | 2008-05-06 | 2011-08-04 | ニューヨーク ブラッド センター, インコーポレイテッド | 抗ウイルス細胞透過性ペプチド |
| CN102197046A (zh) * | 2008-09-22 | 2011-09-21 | 爱勒让治疗公司 | 拟肽大环化合物 |
| JP2012515172A (ja) | 2009-01-14 | 2012-07-05 | エルロン・セラピューティクス・インコーポレイテッド | ペプチド模倣大環状分子 |
| KR102104762B1 (ko) | 2010-08-13 | 2020-04-24 | 에일러론 테라퓨틱스 인코포레이티드 | 펩티도미메틱 거대고리 |
| TW201806968A (zh) | 2011-10-18 | 2018-03-01 | 艾利倫治療公司 | 擬肽巨環化合物 |
| CA2864120A1 (en) | 2012-02-15 | 2013-08-22 | Aileron Therapeutics, Inc. | Triazole-crosslinked and thioether-crosslinked peptidomimetic macrocycles |
| NZ627528A (en) | 2012-02-15 | 2016-05-27 | Aileron Therapeutics Inc | Peptidomimetic macrocycles |
| BR112015009470A2 (pt) | 2012-11-01 | 2019-12-17 | Aileron Therapeutics Inc | aminoácidos dissubstituídos e seus métodos de preparação e uso |
| US11039620B2 (en) | 2014-02-19 | 2021-06-22 | Corning Incorporated | Antimicrobial glass compositions, glasses and polymeric articles incorporating the same |
| US11039621B2 (en) | 2014-02-19 | 2021-06-22 | Corning Incorporated | Antimicrobial glass compositions, glasses and polymeric articles incorporating the same |
| US9622483B2 (en) | 2014-02-19 | 2017-04-18 | Corning Incorporated | Antimicrobial glass compositions, glasses and polymeric articles incorporating the same |
| KR20170058424A (ko) | 2014-09-24 | 2017-05-26 | 에일러론 테라퓨틱스 인코포레이티드 | 펩티드모방 거대고리 및 이의 용도 |
| MX389354B (es) | 2014-09-24 | 2025-03-20 | Aileron Therapeutics Inc | Macrociclos peptidomimeticos y formulaciones de los mismos. |
| WO2016085280A1 (ko) * | 2014-11-28 | 2016-06-02 | 서울대학교산학협력단 | 세포 투과성 스테이플 펩타이드, 이의 제조방법 및 그 용도 |
| SG11201707750YA (en) | 2015-03-20 | 2017-10-30 | Aileron Therapeutics Inc | Peptidomimetic macrocycles and uses thereof |
| WO2017004548A1 (en) | 2015-07-01 | 2017-01-05 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| WO2017018595A1 (ko) * | 2015-07-28 | 2017-02-02 | 동국대학교 산학협력단 | 이중 스테이플화된 펩타이드 및 이의 용도 |
| US10023613B2 (en) | 2015-09-10 | 2018-07-17 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles as modulators of MCL-1 |
| WO2019133179A2 (en) * | 2017-12-01 | 2019-07-04 | Massachusetts Institute Of Technology | Solution-phase affinity selection of inhibitors from combinatorial peptide libraries |
| US20200102356A1 (en) * | 2018-10-01 | 2020-04-02 | NMC Inc. | Compositions and Methods for the Treatment of Huanglongbing (HLB) aka Citrus Greening in Citrus Plants |
| WO2022036049A2 (en) * | 2020-08-12 | 2022-02-17 | New York Blood Center, Inc. | Antiviral stapled peptides against sars-cov-2 |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6187548B1 (en) * | 1993-05-23 | 2001-02-13 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Methods using human calcium sensor protein, fragments thereof and DNA encoding same |
| US6239270B1 (en) * | 1993-05-24 | 2001-05-29 | Rhone-Poulenc Rorer S.A. | Nucleic acids encoding human calcium sensor protein |
| JP4892134B2 (ja) * | 1999-04-09 | 2012-03-07 | ファルマシア・アンド・アップジョン・カンパニー・エルエルシー | 抗菌ワクチン組成物 |
| US6790950B2 (en) * | 1999-04-09 | 2004-09-14 | Pharmacia & Upjohn Company | Anti-bacterial vaccine compositions |
| US7192713B1 (en) | 1999-05-18 | 2007-03-20 | President And Fellows Of Harvard College | Stabilized compounds having secondary structure motifs |
| US6653102B2 (en) * | 2000-10-17 | 2003-11-25 | Myriad Genetics, Inc. | Nucleic acid encoding a phosphatase 2C that interacts with Fe 65 |
| PT2332968T (pt) | 2003-11-05 | 2016-08-17 | Harvard College | Péptidos alfa-helicoidais adequados para a activação ou inibição da morte celular |
| WO2008009000A2 (en) * | 2006-07-13 | 2008-01-17 | Cell Signaling Technology, Inc. | Reagents for the detection of protein phosphorylation in signaling pathways |
| US20100151483A1 (en) * | 2006-07-13 | 2010-06-17 | Cell Signaling Technology, Inc. | Reagents for the detection of protein phosphorylation in signaling pathways |
| KR20090059148A (ko) * | 2006-09-11 | 2009-06-10 | 더 보드 오브 트러스티즈 오브 더 유니버시티 오브 일리노이 | 쿠프레독신 유래된 펩티드의 변형 및 이의 이용 방법 |
| EP2118123B1 (en) | 2007-01-31 | 2015-10-14 | Dana-Farber Cancer Institute, Inc. | Stabilized p53 peptides and uses thereof |
| JP5078401B2 (ja) * | 2007-03-27 | 2012-11-21 | 株式会社Adeka | 防水シート |
| CA2700925C (en) | 2007-09-26 | 2016-08-23 | Dana Farber Cancer Institute | Methods and compositions for modulating bcl-2 family polypeptides |
| EP2247606B1 (en) | 2008-01-23 | 2019-08-21 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for the treatment of viral infections |
| JP2011522796A (ja) * | 2008-05-06 | 2011-08-04 | ニューヨーク ブラッド センター, インコーポレイテッド | 抗ウイルス細胞透過性ペプチド |
| EP2338056B1 (en) | 2008-10-10 | 2018-01-03 | Dana Farber Cancer Institute | Chemical modulators of pro-apoptotic bax and bcl-2 polypeptides |
-
2007
- 2007-10-02 EP EP07839140A patent/EP2073829B1/en not_active Not-in-force
- 2007-10-02 EP EP20120169140 patent/EP2517720A1/en not_active Ceased
- 2007-10-02 JP JP2009531418A patent/JP2010505831A/ja active Pending
- 2007-10-02 WO PCT/US2007/021156 patent/WO2008045238A2/en not_active Ceased
- 2007-10-02 CA CA002665186A patent/CA2665186A1/en not_active Abandoned
- 2007-10-02 ES ES07839140T patent/ES2387827T3/es active Active
- 2007-10-02 AU AU2007307254A patent/AU2007307254A1/en not_active Abandoned
- 2007-10-02 US US12/438,414 patent/US8940864B2/en active Active
-
2009
- 2009-02-20 ZA ZA200901248A patent/ZA200901248B/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ZA200901248B (en) | 2010-04-28 |
| AU2007307254A1 (en) | 2008-04-17 |
| EP2073829A2 (en) | 2009-07-01 |
| WO2008045238A3 (en) | 2008-07-24 |
| EP2073829A4 (en) | 2010-03-03 |
| WO2008045238A2 (en) | 2008-04-17 |
| ES2387827T3 (es) | 2012-10-02 |
| EP2517720A1 (en) | 2012-10-31 |
| US20100130430A1 (en) | 2010-05-27 |
| US8940864B2 (en) | 2015-01-27 |
| EP2073829B1 (en) | 2012-06-20 |
| JP2010505831A (ja) | 2010-02-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8940864B2 (en) | Stabilized therapeutic small helical antiviral peptides | |
| Zhang et al. | A cell-penetrating helical peptide as a potential HIV-1 inhibitor | |
| AU2009244400B2 (en) | Antiviral cell penetrating peptides | |
| DK2320927T3 (en) | Modified peptides as potent inhibitors of the PSD-95 / NMDA receptor interaction | |
| JP2011522796A5 (enExample) | ||
| CN117157305A (zh) | 抗感染的双环肽配体 | |
| CN111643656A (zh) | 广谱冠状病毒膜融合抑制剂及其抗艾滋病病毒的应用 | |
| CN106749558B (zh) | 广谱抑制hiv的脂肽、其衍生物、其药物组合物及其用途 | |
| EP4274839A1 (en) | Anti-infective bicyclic peptide ligands | |
| US8937154B2 (en) | Stabilized therapeutic small helical antiviral peptides | |
| WO2013075594A1 (zh) | 人工设计的抗hiv感染多肽、组合物以及用途 | |
| US20240091368A1 (en) | Anti-infective bicyclic peptide ligands | |
| EP4274841A1 (en) | Anti-infective bicyclic peptide ligands | |
| US20200115418A1 (en) | Anti-hiv peptides | |
| AU2012200580A1 (en) | Stabilized therapeutic small helical antiviral peptides | |
| WO2007068163A1 (en) | Hiv fusion inhibitor peptides and use thereof | |
| CA2766417A1 (en) | Stabilized therapeutic small helical antiviral peptides | |
| US20250325672A1 (en) | Anti-infective bicyclic peptide ligands | |
| WO2016094518A2 (en) | Novel cyclic peptides and methods using same | |
| WO2012139519A1 (zh) | 环肽及其医药用途 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| EEER | Examination request |
Effective date: 20121001 |
|
| FZDE | Dead |
Effective date: 20131002 |