BRPI0914684B1 - Uso de hsp70 ou um fragmento funcional ou variante do mesmo, e, hsp70 ou um fragmento funcional ou variante do mesmomesmo, e, hsp70 ou um fragmento funcional ou variante do mesmo - Google Patents
Uso de hsp70 ou um fragmento funcional ou variante do mesmo, e, hsp70 ou um fragmento funcional ou variante do mesmomesmo, e, hsp70 ou um fragmento funcional ou variante do mesmo Download PDFInfo
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- BRPI0914684B1 BRPI0914684B1 BRPI0914684-9A BRPI0914684A BRPI0914684B1 BR PI0914684 B1 BRPI0914684 B1 BR PI0914684B1 BR PI0914684 A BRPI0914684 A BR PI0914684A BR PI0914684 B1 BRPI0914684 B1 BR PI0914684B1
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- Prior art keywords
- hsp70
- variant
- disease
- lysosomal
- functional fragment
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Abstract
Description
Definições e abreviações
aSMase / ASM Esfingomielinase ácida
ADD70: isca derivada de AIF para Hsp70
AIF: Fator indutor de apoptose
AO: Laranja de Acridina
Apaf-1: fator ativador de protease apoptótica 1
Bag-1: Atanogene-1 associado a Bcl-2
Bcl-2: Linfoma/leucemia de célula B 2
Bid: agonista de morte do domínio que interage BH3
BMP: Bis(monoacilglicero)fosfato
CARD: Domínio de recrutamento de Caspase
Caspase: Protease específica da Cisteína aspartato
CHIP: Terminal carbóxi da proteína de ligação de Hsp70
CytC: Citocromo C
DD: Domínio de morte
DED: Domínio efetor de morte
dsRNA: RNA de filamento duplo
eHsp70: Hsp70 extracelular
ER: Retículo endoplasmático
ERT Terapia de reposição de enzima
FADD: Proteína que contém domínio de morte associado a Fas
HIP: Hsp70 que interage proteína
HRP: Rábano peroxidase
HS: Choque térmico/estresse
HSE: Elemento de choque térmico
HSF: Fator de choque térmico
Hsp: Proteína de choque térmico
HspBP1: Proteína 1 que liga a proteína de choque térmico
IAP: Inibidor da proteína de apoptose
iMEF Fibroblastos Embrionários de Murino Imortalizados
JNK: cinase de terminal NH2 c-jun
LAMP-1 /-2: proteína de membrana associada a lisossoma -1/-2
LBPA: Ácido lisobisfosfatídico
LEDGF: Fator de crescimento derivado de epitélio de lente
LMP: Permeabilização da membrana lisossômica
MIC-1: Citocina 1 inibidora de macrófago
MOMP: Permeabilização da membrana externa mitocondrial
MPR receptor da manose 6-fosfato
MTT: brometo de 3-(4,5-Dimetil-2-tiazolil)-2,5-difenil-2H-tetrazólio
NPD doença de Niemann-Pick
NPDA doença de Niemann-Pick, tipo A
NPDB doença de Niemann-Pick, tipo B
NPDC doença de Niemann-Pick, tipo C
NPDD doença de Niemann-Pick, tipo D
PCD: Morte celular programada
PKC: Proteína cinase C
POPC: Palmitoil-oleoil-fosfatidilcolina
POPS: Palmitoil-oleoil-fosfatidilserina
RNAi: interferência de RNA
ROS: Espécies de oxigênio reativo
SD: Desvio padrão
siRNA: RNA interferente curto
Smac/Diablo: Ativador derivado de mitocôndria secundário de caspases
tBid: Bid truncado
TNF: Fator de necrose de tumor
TNFR: receptor de TNF
TRADD: proteína do domínio de morte associada a TNFR
TRAF: Fator associado a TNFR
Aminoácidos tendo cadeias laterais polares (Asp, Glu, Lys, Arg, His, Asn, Gln, Ser, Thr, Tyr e Cys)
Aminoácidos tendo cadeias laterais não polares (Gly, Ala, Val, Leu, Ile, Phe, Trp, Pro e Met)
Aminoácidos tendo cadeias laterais alifáticas (Gly, Ala, Val, Leu, Ile)
Aminoácidos tendo cadeias laterais cíclicas (Phe, Tyr, Trp, His, Pro)
Aminoácidos tendo cadeias laterais aromáticas (Phe, Tyr, Trp)
Aminoácidos tendo cadeias laterais ácidas (Asp, Glu)
Aminoácidos tendo cadeias laterais básicas (Lys, Arg, His)
Aminoácidos tendo cadeias laterais de amida (Asn, Gln)
Aminoácidos tendo cadeias laterais de hidróxi (Ser, Thr)
Aminoácidos tendo cadeias laterais que contém enxofre (Cys, Met),
Aminoácidos neutros, fracamente hidrofóbicos (Pro, Ala, Gly, Ser, Thr)
Aminoácidos hidrofílicos, ácidos (Gln, Asn, Glu, Asp), e
Aminoácidos hidrofóbicos (Leu, Ile, Val)
- - distúrbios de armazenagem de lipídeo (ou lipidoses), principalmente esfingolipidoses (incluindo Doença de Gaucher e de NiemannPick)
- - gangliosidose (incluindo doença de Tay-Sachs)
- - leucodistrofias
- - mucopolissacaridoses (incluindo síndrome de Hunter e doença de Hurler)
- - distúrbios de armazenagem de glicoproteína (glicoproteinose)
- - mucolipidoses
população judia de Ashkenazi (NPDA e NPDB)
população do Canadá Francês de Nova Escócia (tipo D – agora considerada uma variante de NPDC)
região do Maghreb (Tunísia, Morrocos e Algéria) da África do Norte (NPDB)
população hipano-Americana do Novo México meridional e Colorado (NPDC)
Primeiramente antes de tudo, a ERT é uma forma muito cara de terapia, que é uma carga finaceira para a sociedade e a torna inacessível a alguns pacientes. Também, a ERT é alvejada especificamente apenas a uma doença. Alguns efeitos colaterais foram relatados para Cerezyme®, incluindo o desenvolvimento de uma resposta imune, náusea, vômito, dor abdominal, diarréia, brotoeja, fadiga, dor de cabeça, febre, vertigem, calafrios, dor lombar e frequência cardíaca rápida assim como sintomas sugestivos de reações alérgicas.
MAKAAAIGIDLGTTYSCVGVFQHGKVEIIANDQGNRTTPSYVAFTDTERLIGDAAKNQVALNPQNTVFDAKRL IGRKFGDPVVQSDMKHWPFQVINDGDKPKVQVSYKGETKAFYPEEISSMVLTKMKEIAEAYLGYPVTNAVITV PAYFNDSQRQATKDAGVIAGLNVLRIINEPTAAAIAYGLDRTGKGERNVLIFDLGGGTFDVSILTIDDGIFEV KATAGDTHLGGEDFDNRLVNHFVEEFKRKHKKDISQNKRAVRRLRTACERAKRTLSSSTQASLEIDSLFEGID FYTSITRARFEELCSDLFRSTLEPVEKALRDAKLDKAQIHDLVLVGGSTRIPKVQKLLQDFFNGRDLNKSINP DEAVAYGAAVQAAILMGDKSENVQDLLLLDVAPLSLGLETAGGVMTALIKRNSTIPTKQTQIFTTYSDNQPGV LIQVYEGERAMTKDNNLLGRFELSGIPPAPRGVPQIEVTFDIDANGILNVTATDKSTGKANKITITNDKGRLS KEEIERMVQEAEKYKAEDEVQRERVSAKNALESYAFNMKSAVEDEGLKGKISEADKKKVLDKCQEVISWLDAN TLAEKDEFEHKRKELEQVCNPIISGLYQGAGGPGPGGFGAQGPKGGSGSGPTIEEVD
1 ataaaagccc aggggcaagc ggtccggata acggctagcc tgaggagctg ctgcgacagt
61 ccactacctt tttcgagagt gactcccgtt gtcccaaggc ttcccagagc gaacctgtgc
121 ggctgcaggc accggcgcgt cgagtttccg gcgtccggaa ggaccgagct cttctcgcgg
181 atccagtgtt ccgtttccag cccccaatct cagagcggag ccgacagaga gcagggaacc
241 ggcatggcca aagccgcggc gatcggcatc gacctgggca ccacctactc ctgcgtgggg
301 gtgttccaac acggcaaggt ggagatcatc gccaacgacc agggcaaccg caccaccccc
361 agctacgtgg ccttcacgga caccgagcgg ctcatcgggg atgcggccaa gaaccaggtg
421 gcgctgaacc cgcagaacac cgtgtttgac gcgaagcggc tgattggccg caagttcggc
481 gacccggtgg tgcagtcgga catgaagcac tggcctttcc aggtgatcaa cgacggagac
541 aagcccaagg tgcaggtgag ctacaagggg gagaccaagg cattctaccc cgaggagatc
601 tcgtccatgg tgctgaccaa gatgaaggag atcgccgagg cgtacctggg ctacccggtg
661 accaacgcgg tgatcaccgt gccggcctac ttcaacgact cgcagcgcca ggccaccaag
721 gatgcgggtg tgatcgcggg gctcaacgtg ctgcggatca tcaacgagcc cacggccgcc
781 gccatcgcct acggcctgga cagaacgggc aagggggagc gcaacgtgct catctttgac
841 ctgggcgggg gcaccttcga cgtgtccatc ctgacgatcg acgacggcat cttcgaggtg
901 aaggccacgg ccggggacac ccacctgggt ggggaggact ttgacaacag gctggtgaac
961 cacttcgtgg aggagttcaa gagaaaacac aagaaggaca tcagccagaa caagcgagcc
1021 gtgaggcggc tgcgcaccgc ctgcgagagg gccaagagga ccctgtcgtc cagcacccag
1081 gccagcctgg agatcgactc cctgtttgag ggcatcgact tctacacgtc catcaccagg
1141 gcgaggttcg aggagctgtg ctccgacctg ttccgaagca ccctggagcc cgtggagaag
1201 gctctgcgcg acgccaagct ggacaaggcc cagattcacg acctggtcct ggtcgggggc
1261 tccacccgca tccccaaggt gcagaagctg ctgcaggact tcttcaacgg gcgcgacctg
1321 aacaagagca tcaaccccga cgaggctgtg gcctacgggg cggcggtgca ggcggccatc
1381 ctgatggggg acaagtccga gaacgtgcag gacctgctgc tgctggacgt ggctcccctg
1441 tcgctggggc tggagacggc cggaggcgtg atgactgccc tgatcaagcg caactccacc
1501 atccccacca agcagacgca gatcttcacc acctactccg acaaccaacc cggggtgctg
1561 atccaggtgt acgagggcga gagggccatg acgaaagaca acaatctgtt ggggcgcttc
1621 gagctgagcg gcatccctcc ggcccccagg ggcgtgcccc agatcgaggt gaccttcgac
1681 atcgatgcca acggcatcct gaacgtcacg gccacggaca agagcaccgg caaggccaac
1741 aagatcacca tcaccaacga caagggccgc ctgagcaagg aggagatcga gcgcatggtg
1801 caggaggcgg agaagtacaa agcggaggac gaggtgcagc gcgagagggt gtcagccaag
1861 aacgccctgg agtcctacgc cttcaacatg aagagcgccg tggaggatga ggggctcaag
1921 ggcaagatca gcgaggcgga caagaagaag gtgctggaca agtgtcaaga ggtcatctcg
1981 tggctggacg ccaacacctt ggccgagaag gacgagtttg agcacaagag gaaggagctg
2041 gagcaggtgt gtaaccccat catcagcgga ctgtaccagg gtgccggtgg tcccgggcct
2101 gggggcttcg gggctcaggg tcccaaggga gggtctgggt caggccccac cattgaggag
2161 gtagattagg ggcctttcca agattgctgt ttttgttttg gagcttcaag actttgcatt
2221 tcctagtatt tctgtttgtc agttctcaat ttcctgtgtt tgcaatgttg aaattttttg
2281 gtgaagtact gaacttgctt tttttccggt ttctacatgc agagatgaat ttatactgcc
2341 atcttacgac tatttcttct ttttaataca cttaactcag gccatttttt aagttggtta
2401 cttcaaagta aataaacttt aaaattcaaa aaaaaaaaaa aaaaa
1 ggaaaacggc cagcctgagg agctgctgcg agggtccgct tcgtctttcg agagtgactc
61 ccgcggtccc aaggctttcc agagcgaacc tgtgcggctg caggcaccgg cgtgttgagt
121 ttccggcgtt ccgaaggact gagctcttgt cgcggatccc gtccgccgtt tccagccccc
181 agtctcagag cggagcccac agagcagggc accggcatgg ccaaagccgc ggcgatcggc
241 atcgacctgg gcaccaccta ctcctgcgtg ggggtgttcc aacacggcaa ggtggagatc
301 atcgccaacg accagggcaa ccgcaccacc cccagctacg tggccttcac ggacaccgag
361 cggctcatcg gggatgcggc caagaaccag gtggcgctga acccgcagaa caccgtgttt
421 gacgcgaagc ggctgatcgg ccgcaagttc ggcgacccgg tggtgcagtc ggacatgaag
481 cactggcctt tccaggtgat caacgacgga gacaagccca aggtgcaggt gagctacaag
541 ggggagacca aggcattcta ccccgaggag atctcgtcca tggtgctgac caagatgaag
601 gagatcgccg aggcgtacct gggctacccg gtgaccaacg cggtgatcac cgtgccggcc
661 tacttcaacg actcgcagcg ccaggccacc aaggatgcgg gtgtgatcgc ggggctcaac
721 gtgctgcgga tcatcaacga gcccacggcc gccgccatcg cctacggcct ggacagaacg
781 ggcaaggggg agcgcaacgt gctcatcttt gacctgggcg ggggcacctt cgacgtgtcc
841 atcctgacga tcgacgacgg catcttcgag gtgaaggcca cggccgggga cacccacctg
901 ggtggggagg actttgacaa caggctggtg aaccacttcg tggaggagtt caagagaaaa
961 cacaagaagg acatcagcca gaacaagcga gccgtgaggc ggctgcgcac cgcctgcgag
1021 agggccaaga ggaccctgtc gtccagcacc caggccagcc tggagatcga ctccctgttt
1081 gagggcatcg acttctacac gtccatcacc agggcgaggt tcgaggagct gtgctccgac
1141 ctgttccgaa gcaccctgga gcccgtggag aaggctctgc gcgacgccaa gctggacaag
1201 gcccagattc acgacctggt cctggtcggg ggctccaccc gcatccccaa ggtgcagaag
1261 ctgctgcagg acttcttcaa cgggcgcgac ctgaacaaga gcatcaaccc cgacgaggct
1321 gtggcctacg gggcggcggt gcaggcggcc atcctgatgg gggacaagtc cgagaacgtg
1381 caggacctgc tgctgctgga cgtggctccc ctgtcgctgg ggctggagac ggccggaggc
1441 gtgatgactg ccctgatcaa gcgcaactcc accatcccca ccaagcagac gcagatcttc
1501 accacctact ccgacaacca acccggggtg ctgatccagg tgtacgaggg cgagagggcc
1561 atgacgaaag acaacaatct gttggggcgc ttcgagctga gcggcatccc tccggccccc
1621 aggggcgtgc cccagatcga ggtgaccttc gacatcgatg ccaacggcat cctgaacgtc
1681 acggccacgg acaagagcac cggcaaggcc aacaagatca ccatcaccaa cgacaagggc
1741 cgcctgagca aggaggagat cgagcgcatg gtgcaggagg cggagaagta caaagcggag
1801 gacgaggtgc agcgcgagag ggtgtcagcc aagaacgccc tggagtccta cgccttcaac
1861 atgaagagcg ccgtggagga tgaggggctc aagggcaaga tcagcgaggc ggacaagaag
1921 aaggttctgg acaagtgtca agaggtcatc tcgtggctgg acgccaacac cttggccgag
1981 aaggacgagt ttgagcacaa gaggaaggag ctggagcagg tgtgtaaccc catcatcagc
2041 ggactgtacc agggtgccgg tggtcccggg cctggcggct tcggggctca gggtcccaag
2101 ggagggtctg ggtcaggccc taccattgag gaggtggatt aggggccttt gttctttagt
2161 atgtttgtct ttgaggtgga ctgttgggac tcaaggactt tgctgctgtt ttcctatgtc
2221 atttctgctt cagctctttg ctgcttcact tctttgtaaa gttgtaacct gatggtaatt
2281 agctggcttc attatttttg tagtacaacc gatatgttca ttagaattct ttgcatttaa
2341 tgttgatact gtaagggtgt ttcgttccct ttaaatgaat caacactgcc accttctgta
2401 cgagtttgtt tgtttttttt tttttttttt ttttttgctt ggcgaaaaca ctacaaaggc
2461 tgggaatgta tgtttttata atttgtttat ttaaatatga aaaataaaat gttaaacttt
2521 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa a
No mesmo estudo, a sobrevivência aumentada de células neuronais sensoriais do gânglio da raiz dorsal também foram observados na administração de Hsp70, embora isto dependesse de doses levemente mais altas de Hsp70 do que nos neurônios motores. Além disso, eHsp70 foi mostrada proteger os neurônios motores de outro modo destinados a morrer durante o desenvolvimento embrionário de pinto e também proteger neurônios motores isolados das medulas espinhais de pinto no esgotamento de fator trófico. Um papel de proteção in vivo para eHsp70 também foi descrito quando foi descoberto o dano da retina. Neste estudo, Yu et al., intravitrealmente injetaram uma solução de Hsp70 e Hsc70 recombinantes depois da exposição à luz que induz dano em uma dose que foi previamente descrita causar degeneração fotorreceptora extensiva. De modo interessante, a presença da mistura de eHsp70 na câmara vítrea do olho direito resultou significantemente em mais fotorreceptores sobrevivendo na retina. Além disso, a avaliação da captação de Hsc/Hsp70 rotulados com fluoresceína demonstrou que a mesma foi presente na retina 6 h depois da administração. Hsp70 extracelular administrada via tratamento intranasal também mostrou prevenir as consequências de estresse inevitáveis em ratos e foi recentemente descrito que Hsp70 recombinante humano intraperitonealmente injetado foi eficaz em aumentar a expectativa de vida, retardar o início do sintoma, preservar a função motora e prolongar a sobrevivência de neurônio motor em um modelo de camundongo de esclerose lateral amiotrófica. Trabalho in vitro adicional usando Hsp70 ou a mistura de Hsc/Hsp70 em sistemas neuronais tem além disso mostrado que eHsp70 pode intensificar a tolerância ao estresse de célula neuronal e reduzir a toxicidade da poliglutamina e agregação.
- - Hsp70, ou um fragmento funcional ou variante desta
- - indutores ou co-indutores de Hsp70
- - Medicamentos de molécula pequena tais como Bimoclomol e Arimoclomol
- - Fluidizadores de membrana tais como álcool benzílico
- - Terapia térmica sub-letal (42 °C) ou hipertermia
- - Certos medicamentos do grupo de medicamentos anti-inflamatórios e anti-neoplásticos
- - Estresse celular
- - Espécies de oxigênio reativo (ROS)
- - Adrenalina, noradrenalina
- - Luz UV
- - Terapia de radiação
Arimoclomol é propriedade da CytRx Corporation.
administrar um agente bioativo capaz de aumentar a concentração e/ou atividade intracelulares de Hsp70, e
permitir a interação entre BMP e Hsp70, e
modular a atividade enzimática de uma enzima que interage com BMP.
administrar o agente bioativo de acordo com a presente invenção,
permitir a interação entre BMP e Hsp70, e modular a atividade enzimática de uma enzima que interage com BMP.
ITENS
- 1. Método para modular a atividade enzimática de uma enzima, em que a dita enzima interage com BMP, o dito método compreendendo a etapa de administrar Hsp70, ou um fragmento funcional deste, em uma forma adequada para permitir a interação entre BMP e Hsp70, ou o dito fragmento funcional deste e deste modo modular a atividade enzimática de uma enzima que interage com BMP.
- 2. Método do item 1, em que Hsp70 ou o dito fragmento funcional deste forma um complexo covalente ou não covalente com BMP.
- 3. Método de qualquer um dos itens precedentes, em que BMP interage com uma saposina.
- 4. Método do item 3, em que a dita saposina é selecionada do grupo que consiste de saposina A, saposina B, saposina C e saposina D.
- 5. Método de qualquer um dos itens precedentes, em que a dita enzima é selecionada do grupo que consiste de esfingomielinase, esfingomielinase ácida, sialidase, alfa-galactosidase, beta-galactosidase, beta-galactosilceremidase, glicosilceremidase e ceremidase ácida.
- 6. Hsp70, ou um fragmento funcional desta, para o uso como um medicamento.
- 7. Hsp70, ou um fragmento funcional deste, para o uso no tratamento, alívio, ou profilaxia de um distúrbio de armazenagem lisossômica.
- 8. Uso do item 7, em que o dito distúrbio de armazenagem lisossômica é selecionado do grupo que consiste dos distúrbios de Niemann-Pick, Gaucher, Farber, Krabbe, Fabry e Sialidose.
- 9. Um método para aumentar a captação de um composto, o dito método compreendendo a etapa de administrar o dito composto junto com Hsp70 ou um fragmento funcional deste.
- 10. Método do item 9, em que a dita Hsp70 ou um fragmento funcional desta são covalentemente ligados ao dito composto.
Claims (14)
- Uso de Hsp70, ou um fragmento funcional ou variante do mesmo, caracterizado pelo fato de ser para manufatura de um medicamento para o tratamento de um distúrbio de armazenamento lisossômico, em que o dito Hsp70, ou um fragmento funcional ou variante do mesmo é selecionado do grupo consistindo de SEQ ID NO: 1 e SEQ ID NO: 3.
- Uso de Hsp70, ou um fragmento funcional ou variante do mesmo, de acordo com a reivindicação 1, caracterizado pelo fato de que o dito Hsp70, ou um fragmento funcional ou variante do mesmo, tem 100 % de homologia com a proteína de Hsp70 do tipo selvagem.
- Uso de Hsp70, ou um fragmento funcional ou variante do mesmo, de acordo com a reivindicação 1, caracterizado pelo fato de que o dito Hsp70, ou um fragmento ou variante do mesmo é Hsp70.
- Uso de Hsp70, ou um fragmento funcional ou variante do mesmo, de acordo com a reivindicação 3, caracterizado pelo fato de que o dito Hsp70 é Hsp70 de comprimento total.
- Uso de Hsp70, ou um fragmento funcional ou variante do mesmo, de acordo com a reivindicação 1, caracterizado pelo fato de que o dito Hsp70 ou fragmento funcional ou variante de Hsp70 compreende todos ou parte do domínio de ATPase de Hsp70.
- Uso de Hsp70, ou um fragmento funcional ou variante do mesmo de acordo com a reivindicação 1, caracterizado pelo fato de que o dito Hsp70 ou fragmento funcional ou variante de Hsp70 compreende triptofano na posição de aminoácido de 90 do domínio de ATPase de Hsp70.
- Uso de Hsp70, ou um fragmento funcional ou variante do mesmo de acordo com a reivindicação 1, caracterizado pelo fato de que o dito distúrbio de armazenamento lisossômico é selecionado do grupo que consiste dos distúrbios de Niemann-Pick, Farber, Krabbe, Fabry, Gaucher, Sialidose, Leucodistrofia Metacromática e deficiência de saposina.
- Uso de Hsp70, ou um fragmento funcional ou variante do mesmo de acordo com a reivindicação 1, caracterizado pelo fato de que o dito distúrbio de armazenamento lisossômico é a doença de Niemann-Pick tipo A ou tipo B.
- Uso de Hsp70, ou um fragmento funcional ou variante do mesmo de acordo com a reivindicação 1, caracterizado pelo fato de que a dita doença de armazenamento lisossômico é caracterizada como tendo atividade enzimática residual da enzima defeituosa envolvida na patologia da doença.
- Uso de Hsp70, ou um fragmento funcional ou variante do mesmo de acordo com a reivindicação 9, caracterizado pelo fato de que a dita atividade enzimática residual está na faixa de 0,1 % a 50 %, tal como na faixa de 0,1 a 1 %, por exemplo de 1 a 2 %, tal como de 2 a 3 %, por exemplo de 3 a 4 %, tal como de 4 a 5 %, por exemplo de 5 a 6 %, tal como de 6 a 7 %, por exemplo de 7 a 8 %, tal como de 8 a 9 %, por exemplo de 9 a 10 %, tal como de 10 a 11 %, por exemplo de 11 a 12 %, tal como de 12 a 13 %, por exemplo de 13 a 14 %, tal como de 14 a 15 %, por exemplo de 15 a 20 %, tal como de 20 a 25 %, por exemplo de 25 a 30 %, tal como de 30 a 35 %, por exemplo de 35 a 40 %, tal como de 40 a 45 %, por exemplo na faixa de 45 a 50 % de atividade enzimática residual.
- Uso de acordo com a reivindicação 1, caracterizado pelo fato de que dito Hsp70 ou fragmento funcional ou variante do mesmo é capaz de interagir com BMP (Bis(monoacilglicero)-fosfato).
- Uso de acordo com a reivindicação 1, caracterizado pelo fato de que a referida variante funcional de Hsp70 é um indutor ou co-indutor de Hsp70.
- Uso de acordo com a reivindicação 1, caracterizado pelo fato de que a referida Hsp70 é induzida por um indutor ou co-indutor de Hsp70.
- Uso de acordo com a reivindicação 1, caracterizado pelo fato de que a expressão gênica e a expressão da proteína Hsp70 são amplificadas pelo indutor ou co-indutor de Hsp70.
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