CN101845079B - Hexapeptide or derivative thereof and medical application thereof - Google Patents

Hexapeptide or derivative thereof and medical application thereof Download PDF

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CN101845079B
CN101845079B CN200910131942.2A CN200910131942A CN101845079B CN 101845079 B CN101845079 B CN 101845079B CN 200910131942 A CN200910131942 A CN 200910131942A CN 101845079 B CN101845079 B CN 101845079B
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val
leu
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met
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CN101845079A (en
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刘克良
贾启燕
史卫国
白玉
冯思良
康晓宇
杨琛
张沙
郑保华
姜世勃
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Institute of Pharmacology and Toxicology of AMMS
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Abstract

The invention relates to novel hexapeptide with HIV infection inhibiting activity and derivative thereof, preparation method thereof as well as application of medicine composition containing the hexapeptide or derivative thereof in treating and preventing related disease (such as AIDS) caused by HIV infection.

Description

Six peptide or derivatives thereof and medicinal uses thereof
Technical field
The present invention relates to there is six peptides and the derivative thereof of alleviating or suppressing HIV infection, its preparation method, containing they pharmaceutical composition and they are in treatment or prevention acquired immune deficiency syndrome (AIDS) (acquired immune deficiency syndrome (AIDS) AIDS) and because HIV infects the purposes aspect the relative disease cause.
Background technology
The process of HIV target cell infection, is first the fusion of viral coated film and target cell membrane, and then the genetic material RNA of virus enters in target cell, copies the also virus of release new.It is to be mediated by the acceptor on viral envelope glycoprotein mixture (gp120/gp41) and target cell (CD4 acceptor and Chemokine Receptors CCR-5 or CXCR-4) that HIV enters target cell process.First the CD4 receptors bind on HIV envelope glycoprotein surface subunit gp120 and target cell, is attached on cell; Subsequently again with accessory receptor (chemokine receptor CCR 5 or the CXCR4 etc.) combination of target cell; Cause the conformation of cross-film subunit gp41 to change, the fusogenic peptide of its N end is inserted in host cell membrane, start the fusion of peplos and target cell membrane, complete cell entry host cell course of infection (N Eng1 J Med 2003,348:2228-33).Inhibition to above-mentioned any one link, all can suppress HIV and enter target cell, thus the infection of prevention and treatment HIV.
In recent years, along with deepening continuously of HIV film fusion process Mechanism Study, the Research progress of drugs that inhibition HIV is entered to target cell is very fast.This class medicine is called HIV entry inhibitor.The keying action being risen in film fusion process due to gp41, thereby become the novel targets of inverase research and development.This class be take the medicine that gp41 is action target and is called HIV fusion inhibitor.
2007, Frank Kirchhoff reported that a class has the anti-HIV fusion inhibitor of new role target spot, VIRIP and derivative thereof (Cell, 2007, Vol.129,293-275), and wherein VIRIP has 20 amino acid whose peptides.This compounds can be specifically and fusogenic peptide district (FP) combination of Gp41, thereby the fusion process of blocking-up HIV and host cell suppresses viral copying.
The present invention seeks to searching and there is lower molecular weight, compared with high biological activity, the material of the anti-HIV of better metabolic characteristic.
Summary of the invention
The inventor is discoverable type (I) six peptide or derivatives thereofs after deliberation, and its steric isomer or its pharmaceutical salts have good inhibition HIV target cell infection active.Therefore, formula (I) polypeptide or derivatives thereof, its steric isomer or its salt without physiology toxicity can be used as the infection that medicine is used for the treatment of or prevents HIV.
First aspect present invention relates to the six peptide or derivatives thereofs of formula I, its steric isomer or its pharmaceutical salts:
R 1-AA 1-AA 2-Val-AA 4-Leu-AA 6_ R 2formula (I)
Wherein
AA 1can be natural or non-natural hydrophobic amino acid or the disappearance of D type or L-type;
AA 2can be the natural of D type or L-type or non-natural aromatic amino acid or disappearance;
AA 4can be the natural of D type or L-type or non-natural aromatic amino acid;
AA 6can be natural or alpha-non-natural amino acid or the disappearance of D type or L-type;
R 1h, Ac-, urea groups-or 1-10 amino-acid residue;
R 2be-OH ,-NH2 or 1-10 amino-acid residue;
R 1or R 2can further be amidated, alkylation, acylations, urea groups, PEGization.
Further, in the present invention,
Proline(Pro), oxyproline or the Pyrrolidonecarboxylic acid of the preferred L of AA1 or D type;
AA2 and/or AA4 are preferably the phenylalanine, 4-amino-benzene L-Ala, 4-chlorophenylalanine, naphthylalanine, β-piperonyl L-Ala, morpholine methyl phenylalanine of L or D type or independently of one another to urea groups phenylalanine;
AA6 is preferably methionine(Met), Serine, glutamine, aspartic acid, l-asparagine, Methionin or arginine.
In R1 and R2, amino-acid residue is preferably 1,2,3 or 4, says for example, and it includes but not limited to: aspartic acid, l-asparagine, Isoleucine, L-glutamic acid or glutamine.
R 1it is the sequence of H, Ac-, a Ureido-or 1-10 amino-acid residue;
R 2be-OH, the sequence of-NH2 or 1-10 amino-acid residue;
According to the preferred embodiments of the invention, the present invention's six peptide or derivatives thereofs are selected from peptide or its steric isomer or its pharmaceutical salts below:
(1)Ac-Pro 1-Phe 2-Val 3-Phe 4-Leu 5-Met 6-NH 2
(2)Ac-Pro 1-Phe 2-Val 3-Phe 4-Leu 5-NH 2
(3)Ac-Pro 1-Phe 2-Val 3-Phe 4-NH 2
(4)Ac-Pro 1-Phe 2-Val 3-NH 2
(5)Ac-Phe 1-Val 2-Phe 3-Leu 4-Met 5-NH 2
(6)Ac-Phe 1-Val 2-Phe 3-Leu 4-NH 2
(7)Ac-Phe 1-Val 2-Phe 3-NH 2
(8)Ac-Val 1-Phe 2-Leu 3-Met 4-NH 2
(9)Ac-Val 1-Phe 2-Leu 3-NH 2
(10)Ac-Phe 1-Leu 2-Met 3-NH 2
(11)Ac-D-Pro 1-D-Phe 2-D-Val 3-D-Phe 4-D-Leu 5-D-Met 6-NH 2
(12)Ac-Pro 1-Phe 2-Val 3-Phe 4-Leu 5-Ser 6-NH 2
(13)Ac-Pro 1-Phe 2-Val 3-Phe 4-Leu 5-Gln 6-NH 2
(14)Ac-Pro 1-Phe 2-Val 3-Phe 4-Leu 5-Asp 6-NH 2
(15)Ac-Pro 1-Phe 2-Val 3-Phe 4-Leu 5-Lys 6-NH 2
(16)Ac-Pro 1-Phe 2-Val 3-Phe 4-Leu 5-Asn 6-NH 2
(17)Ac-Pro 1-Nal 2-Val 3-Phe 4-Leu 5-Met 6-NH 2
(18)Ac-Pro 1-Phe 2-Val 3-Nal 4-Leu 5-Met 6-NH 2
(19)Ac-Pro 1-Nal 2-Val 3-Nal 4-Leu 5-Met 6-NH 2
(20)Ac-Pro 1-Mop 2-Val 3-Phe 4-Leu 5-Met 6-NH 2
(21)Ac-Pro 1-Phe 2-Val 3-Mop 4-Leu 5-Met 6-NH 2
(22)Ac-Pro 1-Mop 2-Val 3-Mop 4-Leu 5-Met 6-NH 2
(23)Pgl 1-Phe 2-Val 3-Phe 4-Leu 5-Met 6-NH 2
(24)Ureido-Pro 1-Phe 2-Val 3-Phe 4-Leu 5-Met 6-NH 2
(25)Ac-Pro 1-Phe 2-Val 3-Phe 4-Leu 5-Met 6-Cys 7-OH
(26)Ac-Asp 1-Pro 2-Phe 3-Val 4-Phe 5-Leu 6-Met 7-NH 2
(27)Ac-Asn 1-Pro 2-Phe 3-Val 4-Phe 5-Leu 6-Met 7-NH 2
(28)Ac-Pro 1-Phe 2-Val 3-Phe 4-Leu 5-Met 6-Iln 7-NH 2
(29)Ac-Pro 1-Phe 2-Val 3-Phe 4-Leu 5-Met 6-Iln 7-Glu 8-NH 2
(30)Ac-Pro 1-Phe 2-Val 3-Phe 4-Leu 5-Met 6-Iln 7-Glu 8-Gln 9-NH 2
(31)Ac-Pro 1-Phe 2-Val 3-Phe 4-Leu 5-Met 6-Iln 7-Glu 8-Gln 9-Asn 10-NH 2
(32)Ac-D-Met 1-D-Leu 2-D-Phe 3-D-Val 4-D-Phe 5-D-Pro 6-NH 2
(33)Ac-Pro 1-D-Phe 2-Val 3-D-Phe 4-Leu 5-Met 6-NH 2
The preferred polypeptide of the present invention is numbering (1), (8), (9) and (32) six peptide or derivatives thereofs.
Further aspect of the present invention relates to the pharmaceutical composition containing at least one formula (I) six peptide or derivatives thereofs or their steric isomer or their pharmaceutical salts and pharmaceutically acceptable carrier or vehicle.
The invention still further relates to formula I six peptide or derivatives thereofs or their steric isomer or its pharmaceutical salts purposes in the medicine of preparation treatment or pre-preventing HIV infection relative disease (as acquired immune deficiency syndrome (AIDS)) or symptom.
The preparation method who the invention still further relates to formula I six peptide or derivatives thereofs or its steric isomer or its pharmaceutical salts, the method comprises
Adopt solid phase synthesis process; the Rink Amid resin of take is carrier; Fmoc-protects strategy; DCC/HOBT or HBTU/HOBT are condensation reagent; piperidines/DMF is deprotecting regent; according to the aminoacid sequence of prepared target compound (compound), from C, hold N end, by the Fmoc solid-phase peptide synthesis peptide resin of standard.Above-mentioned peptide resin is put into 250ml eggplant shape glass reaction bottle, under ice bath, add lysate I 10ml, lysate I formula: TFA: methyl-phenoxide: meta-cresol: dithioglycol: water=7.5: 1: 0.5: 0.5: 0.5, ice bath stirs 30 minutes, is raised to room temperature and continues to stir 90 minutes, adds cold anhydrous diethyl ether 100ml, suction filtration obtains white solid, add water and dissolve in right amount, suction filtration, filtrate lyophilize.
Term of the present invention " derivative " comprises formula (I) six peptide disappearances 1,2, or 3 amino acid, or adds 1,2,3 or 4 amino acid at two ends or arbitrary end of six peptides.
Term used herein " steric isomers of formula (I) six peptide or derivatives thereofs " refers to its corresponding D-or L-steric configuration.
In the present invention, polypeptide is generally six peptides, but can have aminoacid deletion in this six peptide, becomes three, four or pentapeptide; Or the one or both ends of appointing at six peptide two ends add 1-10, preferred 1-4 amino acid, becomes seven, eight, nine or decapeptide.
According to the present invention, pharmaceutical composition of the present invention can be by the preparation of this area ordinary method, for example, by formula I six peptide or derivatives thereofs and pharmaceutical carrier or mixed with excipients.In the present invention, pharmaceutical carrier used or vehicle are generally pharmaceutical carrier or the vehicle that pharmacy field is conventional.Formula I polypeptide of the present invention can be used alone or uses with pharmaceutical compositions.Using method can be oral or parenteral route.Oral administration preparation can be tablet, capsule or granule etc.Non-intestinal drug delivery agent can be injection, sprays, patch etc.The present composition also can be made into sustained release preparation, as microballoon etc.
Embodiment
The abbreviation of using in the present invention has implication below:
Ac (Acetyl) ethanoyl
AIDS (Acquired Immure Deficiency Syndrome) acquired immune deficiency syndrome (AIDS),
Acquired immune deficiency syndrome (AIDS)
Ala (Alanine, A) L-Ala
Arg (Arginine, R) arginine
Asn (Asparagine, N) N
Asp (Aspartic acid, D) aspartic acid
Boc (t-Butoxycarbonyl) tertbutyloxycarbonyl
CDI (N, N '-Carbonyldiimidazole) carbonyl dimidazoles
CHR (C-terminal heptad repeat) C-terminal tumor-necrosis factor glycoproteins
Cpa 4-chlorophenylalanine
DCC (N, N-Dicyclohexylcarbodiimide) dicyclohexylcarbodiimide
DCM (Dichloromethane) methylene dichloride
DIEA (N, N-Diisopropylethylamine) DIPEA
DMF (N, N-Dimethyl malonate) dimethyl formamide
Env (envelope glycoprotein) envelope glycoprotein
Fmoc (Fluorenylmethoxycarbonyl) fluorenylmethyloxycarbonyl
Gln (Glutamine, Q) paddy acyl ammonia
Glu (Glutamic acid, E) L-glutamic acid
HBTU 2-(1H-1-hydroxybenzotriazole)-1,1,3,3-tetramethyl-urea phosphofluoric acid
His (Histidine, H) Histidine
HoBt (1-Hydroxylbenzotriazole anhydrous) 1-hydroxy benzo triazole
HIV (Human Immunodeficiency Virus)) human immunodeficiency virus
HIV-1 human immunodeficiency virus I type
HIV-2 human immunodeficiency virus II type
HPLC (High performance liquid chromatography) high performance liquid chromatography
Ile (Isoleucine, I) Isoleucine
Leu (Leucine, L) leucine
Lys (Lysine, K) Methionin
MBHA phenylamino methyl resin
MS mass spectrum
Mob β-piperonyl L-Ala
Mop morpholine methyl phenylalanine
Nal naphthylalanine
NHR (N-terminal heptad repeat) N-terminal tumor-necrosis factor glycoproteins
Phe (Phenylalanine, F) phenylalanine
Ser (Serine, S) Serine
TFA (trifluoroacetic acid) trifluoroacetic acid
TLC (Thin-layer chromatography) thin-layer chromatography
Thr (Threonie, T) Threonine
Trp (Tryptophan, W) tryptophane
Tyr (Tyrosine, Y) tyrosine
Uph (4-Ureido-phenylalanine) 4-urea groups phenylalanine
Embodiment
Example below and biological activity test are used for further illustrating the present invention, but this and do not mean that any limitation of the invention.
Embodiment solid-phase synthesized carrier mbha resin used is the synthetic responsibility of Tianjin Nankai company limited product; DCC, HOBT, HBTU, DIEA and the natural amino acid of Fmoc protection or the alpha-non-natural amino acid of D type are gill biochemical corp, Shanghai and Chengdu Cheng Nuo new technology limited liability company product.
Embodiment 1: compound (1) synthetic
The 0.3g mbha resin (0.48mmol) of take is solid phase carrier, DCC/HOBt or HBTU/DIEA are condensing agent, according to the aminoacid sequence of the formula I polypeptide that will obtain, from C, hold N end, by the Fmoc solid-phase peptide synthesis of standard, (polypeptide is synthetic for reference: Huang Weide, Chen Changqing work, Science Press, 1985) the synthetic Ac-PFVFLM-MBHA resin of operation.
By after methionine(Met), leucine, phenylalanine, α-amino-isovaleric acid, phenylalanine, proline(Pro) successively condensation, with oxalic acid acid anhydride and DIEA end-blocking, above-mentioned peptide resin is put into the reactor of HF cutting device, add 1.0mL methyl-phenoxide, after installing, the system of HF cutting device is evacuated, use cooled with liquid nitrogen reactor, proceed to the liquid HF of about 10mL, in 0 ℃ of reaction 40 minutes.With oil pump, take HF away, take off reactor, add freezing anhydrous diethyl ether to be settled out solid, then suspension is transferred in sand core funnel.With a small amount of cooling anhydrous diethyl ether washing three times, with the aqueous solution, rinse to resin and no longer mutually adheres to, collect washings, must white dry powder after lyophilize.Through RP-HPLC purifying, obtain compound (1) sterling.MS:795.1 (theoretical value: 794).
Embodiment 2: compound (9) synthetic
The 0.25g Rink Amid resin (0.50mmol) of take is solid phase carrier, DCC/HOBt or HBTU/DIEA are condensing agent, according to the aminoacid sequence of prepared compound, from C, hold N end, by the Fmoc solid-phase peptide synthesis of standard, (polypeptide is synthetic for reference: Huang Weide, Chen Changqing work, Science Press, 1985) the synthetic VFL-Rink Amid resin of operation.
By leucine, phenylalanine, α-amino-isovaleric acid is successively after condensation, with oxalic acid acid anhydride and DIEA end-blocking, above-mentioned peptide resin is put into 250ml eggplant shape glass reaction bottle, under ice bath, add lysate I 10ml, lysate I formula: TFA: methyl-phenoxide: meta-cresol: dithioglycol: water=7.5: 1: 0.5: 0.5: 0.5, ice bath stirs 30min, be raised to room temperature and continue to stir 90min, add cold anhydrous diethyl ether 100ml, suction filtration obtains white solid, adding water dissolves in right amount, suction filtration, filtrate lyophilize, obtain white dry powder 0.27g, through RP-HPLC purifying, obtain compound (9) sterling.MS:419.0 (theoretical value 418.5).
Embodiment 3
According to the same procedure of embodiment 9, use the amino acid in corresponding compound number to synthesize following polypeptide:
Compound number MW (mass spectrum result) MW (theoretical value)
2 663.6 662.8
3 548.8 549.7
4 403.2 402.5
5 697.1 696.9
6 566.5 565.7
7 453.2 452.6
8 550.3 549.7
10 451.2 450.6
11 794.5 794
12 750.4 749.9
13 791.6 791
14 777 777.9
15 791.6 791
16 777.5 776.9
20 893.6 893.6
21 893.9 893.6
23 766.5 766.1
25 898.7 898.2
26 908.6 908.1
27 909.5 909.1
28 907.5 907.2
29 1036.7 1036.3
30 1165.0 1164.4
31 1278.1 1278.5
32 794.5 794
33 794.1 794
Embodiment 4: compound (24) synthetic
1. tertiary butyl carboxamide proline(Pro) is synthetic
100ml methyl alcohol is added in eggplant type bottle, ice bath agitation and dropping 7.4ml excess acetyl chloride 30min, remove ice bath and add 4g L-PROLINE (L-PROLINE: Acetyl Chloride 98Min. (mol ratio)=1: 3), 6h is heated up in a steamer in 60 ℃ of oil baths next time, underpressure distillation solvent evaporated, after adding DCM dilution, be spin-dried for, after add ether repeatedly to revolve to steam three times, obtain faint yellow oily matter L-PROLINE methyl ester hydrochloride.Add again 7ml DIPEA (DIEA) and 200ml DCM to stir 10min, obtain proline methyl ester.Extremely clarification in 2.82g carbonyl dimidazoles (CDI) being dissolved in to DCM in eggplant type bottle, under ice bath, drip TERTIARY BUTYL AMINE 2ml (TERTIARY BUTYL AMINE: CDI: L-PROLINE methyl ester hydrochloride=1.1: 1: 2), dropwise stirring reaction 30min under room temperature, obtain tertiary butyl aminocarbonyl imidazoles.In 50 ℃ of oil baths of tertiary butyl aminocarbonyl imidazoles and proline methyl ester, return and heat up in a steamer 8h.Obtain twice of 1N hcl as extraction agent of reaction solution, getting DCM layer water and saturated aqueous common salt respectively extracts one time, after anhydrous magnesium sulfate drying, be spin-dried for solvent, obtain white solid tertiary butyl carboxamide proline methyl ester (M=214) 1.93g (productive rate 52%) Rf=0.61 (DCM: MeOH: HAc=20: 1: 0.5). 1H-NMR(DMSO-D 6，400MHz，δppm)：1.24(S，9H)，1.84(m，3H)，2.05(m，H)，3.35(m，2H)，4.17(d，H，J＝7.2)，5，38(s，H)，12.32(s，H)
2. compound (24) is synthetic
The 0.25g Rink Amid resin (0.50mmol) of take is solid phase carrier, DCC/HOBt or HBTU/DIEA are condensing agent, according to the aminoacid sequence of prepared compound, from C, hold N end, by the Fmoc solid-phase peptide synthesis of standard, (polypeptide is synthetic for reference: Huang Weide, Chen Changqing work, Science Press, 1985) the synthetic Rink Amid resin of operation.
By methionine(Met), leucine, phenylalanine, α-amino-isovaleric acid, phenylalanine, tertiary butyl carboxamide proline(Pro) is successively after condensation, with oxalic acid acid anhydride and DIEA end-blocking, above-mentioned peptide resin is put into 250ml eggplant shape glass reaction bottle, under ice bath, add lysate I 10ml, lysate I formula: TFA: methyl-phenoxide: meta-cresol: dithioglycol: water=7.5: 1: 0.5: 0.5: 0.5, ice bath stirs 30min, be raised to room temperature and continue to stir 90min, add cold anhydrous diethyl ether 100ml, suction filtration obtains white solid, adding water dissolves in right amount, suction filtration, filtrate lyophilize, obtain white dry powder, through RP-HPLC purifying, obtain sterling.MS:(theoretical value).
Embodiment 4: suppress HIV-1 biological activity assay.
HIV-1 copy detection
In MT-2 cell detection, act on the inhibition activity of the polypeptide of the present invention of HIV-1 IIIB mixture.In the RPMI-1640 of the 200 μ L containing 10% foetal calf serum, 1 * 10 4hIV-1 bacterial classification of individual MT-2 cell transfecting (100 TCID50), adds test compounds (blank group is not added) according to the concentration gradient of setting, and spends the night.Afterwards, remove culture supernatant, change the nutrient solution that does not add test compounds.After transfection the 4th day, the culture supernatant of 100 μ l is collected in every hole, adds the 5%Triton X-100 of same volume, by quantitative Elisa method, is detected the output of p24 antigen and is calculated IC50 value.Restructuring p24 protein reagent box is purchased from USBiological (Swampscott, MA).
According to the method described above, determination of activity the results are shown in Table 1
Figure G2009101319422D00101
Figure G2009101319422D00111

Claims (7)

1. be selected from following polypeptide or its pharmaceutical salts:
(1)Ac-Pro 1-Phe 2-Val 3-Phe 4-Leu 5-Met 6-NH 2
(2)Ac-Pro 1-Phe 2-Val 3-Phe 4-Leu 5-NH 2
(6)Ac-Phe 1-Val 2-Phe 3-Leu 4-NH 2
(8)Ac-Val 1-Phe 2-Leu 3-Met 4-NH 2
(9)Ac-Val 1-Phe 2-Leu 3-NH 2
(12)Ac-Pro 1-Phe 2-Val 3-Phe 4-Leu 5-Ser 6-NH 2
(13)Ac-Pro 1-Phe 2-Val 3-Phe 4-Leu 5-Gln 6-NH 2
(14)Ac-Pro 1-Phe 2-Val 3-Phe 4-Leu 5-Asp 6-NH 2
(15)Ac-Pro 1-Phe 2-Val 3-Phe 4-Leu 5-Lys 6-NH 2
(16)Ac-Pro 1-Phe 2-Val 3-Phe 4-Leu 5-Asn 6-NH 2
(20)Ac-Pro 1-Mop 2-Val 3-Phe 4-Leu 5-Met 6-NH 2
(26)Ac-Asp 1-Pro 2-Phe 3-Val 4-Phe 5-Leu 6-Met 7-NH 2
(27)Ac-Asn 1-Pro 2-Phe 3-Val 4-Phe 5-Leu 6-Met 7-NH 2。
2. pharmaceutical composition, the polypeptide that it contains at least one claim 1 or its pharmaceutical salts and pharmaceutically acceptable carrier.
3. pharmaceutical composition, the polypeptide that it contains at least one claim 1 or its pharmaceutical salts and vehicle.
4. the polypeptide of claim 1 or its pharmaceutical salts purposes in the medicine for the preparation for the treatment of or pre-preventing HIV infection relative disease.
5. purposes according to claim 4, it is acquired immune deficiency syndrome (AIDS) that wherein said HIV infects relative disease.
6. following polypeptide or its pharmaceutical salts purposes in the medicine for the preparation for the treatment of or pre-preventing HIV infection relative disease:
Ac-Phe 1-Val 2-Phe 3-Leu 4-Met 5-NH 2。
7. purposes according to claim 6, it is acquired immune deficiency syndrome (AIDS) that wherein said HIV infects relative disease.
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WO2011127624A1 (en) * 2010-04-13 2011-10-20 中国人民解放军军事医学科学院毒物药物研究所 Anti-hiv peptide
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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1377275A (en) * 1999-08-09 2002-10-30 特里帕普股份公司 Peptides that block viral infectivity and methods of use thereof
CN101020710A (en) * 2007-03-05 2007-08-22 浙江大学 Integrase inhibiting peptide and its application in preparing AIDS-treating medicine
CN101088557A (en) * 2006-06-12 2007-12-19 天津市扶素生物技术有限公司 Medicine composition for preventing and treating HIV infection and its application
CN101235083A (en) * 2007-02-02 2008-08-06 同济大学 HIV-I resisting polypeptide, coded sequence and use thereof

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1377275A (en) * 1999-08-09 2002-10-30 特里帕普股份公司 Peptides that block viral infectivity and methods of use thereof
CN101088557A (en) * 2006-06-12 2007-12-19 天津市扶素生物技术有限公司 Medicine composition for preventing and treating HIV infection and its application
CN101235083A (en) * 2007-02-02 2008-08-06 同济大学 HIV-I resisting polypeptide, coded sequence and use thereof
CN101020710A (en) * 2007-03-05 2007-08-22 浙江大学 Integrase inhibiting peptide and its application in preparing AIDS-treating medicine

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
"The SEC Rececptor Recognizes a Pentapeptide Neodomain of α1-Antitrypsin-Protease Complexes";Gregg Joslin et al.,;《The Journal of Biological Chemistry》;19910615;第266卷(第17期);摘要部分 *
Gregg Joslin et al.,."The SEC Rececptor Recognizes a Pentapeptide Neodomain of α1-Antitrypsin-Protease Complexes".《The Journal of Biological Chemistry》.1991,第266卷(第17期),第11282页-第11288页.
Luis Fernando Congote."Serpin A1 and CD91 as host instruments against HIV-1 infection：Are extracellular antiviral peptides acting as intracellular messengers".《Virus Research》.2007,第125卷第119页-第134页.
Luis Fernando Congote."Serpin A1 and CD91 as host instruments against HIV-1 infection:Are extracellular antiviral peptides acting as intracellular messengers".《Virus Research》.2007,第125卷第119页-第134页. *

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Inventor after: Liu Keliang

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