Abstract
Background: There is no effective and safe preventive/therapeutics vaccine against HIV-1 worldwide. Different viral proteins such as Nef, and two regions of Env including; variable loop of gp120 (V3) and membrane proximal external region of gp41 (MPER) are particularly important for vaccine development in different strategies and they are also the primary targets of cellular and humoral immune responses. On the other side, LDP12 is a new cell-penetrating peptide (CPP) which is capable of therapeutic application and cargoes delivery across the cellular membrane.
Objective: In current study, we designed and produced Nef-MPER-V3 fusion protein harboring LDP12 that has the capability of being used in future vaccine studies.
Methods: The CPP-protein was expressed in E. coli Rosseta (DE3) strain and purified through Ni-NTA column. Characterization of cellular delivery and toxicity of the recombinant protein were evaluated by western blotting and MTT assay.
Results: Our results showed that the CPP-protein was successfully expressed and purified with high yield of 5 mg/L. Furthermore, non-cytotoxic effect was observed and specific band (~ 37 KDa) in western blotting indicated the capability of LDP12 to improve the rate of penetration into HEK-293T cells in comparison with a control sample.
Conclusion: Altogether, the data indicated that LDP12 CPP could be utilized to internalize HIV-1 Nef-MPER-V3 protein into eukaryotic cell lines without any toxicity and represented a valuable potential vaccine candidate and this guarantees the further evaluation towards the assessment of its immunogenicity in mice, which is currently under process.
Keywords: Cell penetrating peptide, HIV-1, recombinant protein, Nef-MPER-V3, LDP12, vaccine.
Graphical Abstract
[1]
UNAIDS 2019. Global HIV & AIDS statistics. Available from: http://www.unaids.org/en/resources/factsheet
[2]
Larijani, M.S.; Ramezani, A.; Sadat, S.M. Updated studies on the development of HIV therapeutic vaccine. Curr. HIV Res., 2019, 17(2), 75-84.[http://dx.doi.org/10.2174/1570162X17666190618160608] [PMID: 31210114]
[3]
Burton, D.R.; Mascola, J.R. Antibody responses to envelope glycoproteins in HIV-1 infection. Nat. Immunol., 2015, 16(6), 571-576.[http://dx.doi.org/10.1038/ni.3158] [PMID: 25988889]
[4]
Landi, A.; Iannucci, V.; Nuffel, A.V.; Meuwissen, P.; Verhasselt, B. One protein to rule them all: Modulation of cell surface receptors and molecules by HIV Nef. Curr. HIV Res., 2011, 9(7), 496-504.[http://dx.doi.org/10.2174/157016211798842116] [PMID: 22103833]
[5]
Lai, R.P.J.; Yan, J.; Heeney, J.; McClure, M.O.; Göttlinger, H.; Luban, J.; Pizzato, M. Nef decreases HIV-1 sensitivity to neutralizing antibodies that target the membrane-proximal external region of TMgp41. PLoS Pathog., 2011, 7(12), e1002442.[http://dx.doi.org/10.1371/journal.ppat.1002442] [PMID: 22194689]
[6]
Garcia, J.V.; Miller, A.D. Serine phosphorylation-independent downregulation of cell-surface CD4 by nef. Nature, 1991, 350(6318), 508-511.[http://dx.doi.org/10.1038/350508a0] [PMID: 2014052]
[7]
Aiken, C.; Konner, J.; Landau, N.R.; Lenburg, M.E.; Trono, D. Nef induces CD4 endocytosis: Requirement for a critical dileucine motif in the membrane-proximal CD4 cytoplasmic domain. Cell, 1994, 76(5), 853-864.[http://dx.doi.org/10.1016/0092-8674(94)90360-3] [PMID: 8124721]
[8]
Piguet, V.; Gu, F.; Foti, M.; Demaurex, N.; Gruenberg, J.; Carpentier, J.L.; Trono, D. Nef-induced CD4 degradation: A diacidic-based motif in Nef functions as a lysosomal targeting signal through the binding of beta-COP in endosomes. Cell, 1999, 97(1), 63-73.[http://dx.doi.org/10.1016/S0092-8674(00)80715-1] [PMID: 10199403]
[9]
Schwartz, O.; Maréchal, V.; Le Gall, S.; Lemonnier, F.; Heard, J.M. Endocytosis of major histocompatibility complex class I molecules is induced by the HIV-1 Nef protein. Nat. Med., 1996, 2(3), 338-342.[http://dx.doi.org/10.1038/nm0396-338] [PMID: 8612235]
[10]
Blagoveshchenskaya, A.D.; Thomas, L.; Feliciangeli, S.F.; Hung, C.H.; Thomas, G. HIV-1 Nef downregulates MHC-I by a PACS-1- and PI3K-regulated ARF6 endocytic pathway. Cell, 2002, 111(6), 853-866.[http://dx.doi.org/10.1016/S0092-8674(02)01162-5] [PMID: 12526811]
[11]
Baur, A.S.; Sawai, E.T.; Dazin, P.; Fantl, W.J.; Cheng-Mayer, C.; Peterlin, B.M. HIV-1 Nef leads to inhibition or activation of T cells depending on its intracellular localization. Immunity, 1994, 1(5), 373-384.[http://dx.doi.org/10.1016/1074-7613(94)90068-X] [PMID: 7882168]
[12]
Schrager, J.A.; Marsh, J.W. HIV-1 Nef increases T cell activation in a stimulus-dependent manner. Proc. Natl. Acad. Sci. USA, 1999, 96(14), 8167-8172.[http://dx.doi.org/10.1073/pnas.96.14.8167] [PMID: 10393966]
[13]
Alexander, L.; Du, Z.; Rosenzweig, M.; Jung, J.U.; Desrosiers, R.C. A role for natural simian immunodeficiency virus and human immunodeficiency virus type 1 nef alleles in lymphocyte activation. J. Virol., 1997, 71(8), 6094-6099.[http://dx.doi.org/10.1128/JVI.71.8.6094-6099.1997] [PMID: 9223503]
[14]
Simmons, A.; Aluvihare, V.; McMichael, A. Nef triggers a transcriptional program in T cells imitating single-signal T cell activation and inducing HIV virulence mediators. Immunity, 2001, 14(6), 763-777.[http://dx.doi.org/10.1016/S1074-7613(01)00158-3] [PMID: 11420046]
[15]
Foster, J.L.; Garcia, J.V. HIV-1 Nef: At the crossroads. Retrovirology, 2008, 5(5), 84.[http://dx.doi.org/10.1186/1742-4690-5-84] [PMID: 18808677]
[16]
Geyer, M.; Fackler, O.T.; Peterlin, B.M. Structure--function relationships in HIV-1 Nef. EMBO Rep., 2001, 2(7), 580-585.[http://dx.doi.org/10.1093/embo-reports/kve141] [PMID: 11463741]
[17]
Visciano, M.L.; Diomede, L.; Tagliamonte, M.; Tornesello, M.L.; Asti, V.; Bomsel, M.; Buonaguro, F.M.; Lopalco, L.; Buonaguro, L. Generation of HIV-1 virus-like particles expressing different HIV-1 glycoproteins. Vaccine, 2011, 29(31), 4903-4912.[http://dx.doi.org/10.1016/j.vaccine.2011.05.005] [PMID: 21596074]
[18]
Walker, L.M.; Phogat, S.K.; Chan-Hui, P.Y.; Wagner, D.; Phung, P.; Goss, J.L.; Wrin, T.; Simek, M.D.; Fling, S.; Mitcham, J.L.; Lehrman, J.K.; Priddy, F.H.; Olsen, O.A.; Frey, S.M.; Hammond, P.W.; Kaminsky, S.; Zamb, T.; Moyle, M.; Koff, W.C.; Poignard, P.; Burton, D.R.; Protocol, G. Principal Investigators. Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. Science, 2009, 326(5950), 285-289.[http://dx.doi.org/10.1126/science.1178746] [PMID: 19729618]
[19]
Gorny, M.K.; Williams, C.; Volsky, B.; Revesz, K.; Wang, X.H.; Burda, S.; Kimura, T.; Konings, F.A.; Nádas, A.; Anyangwe, C.A.; Nyambi, P.; Krachmarov, C.; Pinter, A.; Zolla-Pazner, S. Cross-clade neutralizing activity of human anti-V3 monoclonal antibodies derived from the cells of individuals infected with non-B clades of human immunodeficiency virus type 1. J. Virol., 2006, 80(14), 6865-6872.[http://dx.doi.org/10.1128/JVI.02202-05] [PMID: 16809292]
[20]
Corti, D.; Langedijk, J.P.; Hinz, A.; Seaman, M.S.; Vanzetta, F.; Fernandez-Rodriguez, B.M.; Silacci, C.; Pinna, D.; Jarrossay, D.; Balla-Jhagjhoorsingh, S.; Willems, B.; Zekveld, M.J.; Dreja, H.; O’Sullivan, E.; Pade, C.; Orkin, C.; Jeffs, S.A.; Montefiori, D.C.; Davis, D.; Weissenhorn, W.; McKnight, A.; Heeney, J.L.; Sallusto, F.; Sattentau, Q.J.; Weiss, R.A.; Lanzavecchia, A. Analysis of memory B cell responses and isolation of novel monoclonal antibodies with neutralizing breadth from HIV-1-infected individuals. PLoS One, 2010, 5(1), e8805.[http://dx.doi.org/10.1371/journal.pone.0008805] [PMID: 20098712]
[21]
Montero, M.; van Houten, N.E.; Wang, X.; Scott, J.K. The membrane-proximal external region of the human immunodeficiency virus type 1 envelope: Dominant site of antibody neutralization and target for vaccine design. Microbiol. Mol. Biol. Rev., 2008, 72(1), 54-84.[http://dx.doi.org/10.1128/MMBR.00020-07] [PMID: 18322034]
[22]
Muñoz-Barroso, I.; Salzwedel, K.; Hunter, E.; Blumenthal, R. Role of the membrane-proximal domain in the initial stages of human immunodeficiency virus type 1 envelope glycoprotein-mediated membrane fusion. J. Virol., 1999, 73(7), 6089-6092.[http://dx.doi.org/10.1128/JVI.73.7.6089-6092.1999] [PMID: 10364363]
[23]
Salzwedel, K.; West, J.T.; Hunter, E. A conserved tryptophan-rich motif in the membrane-proximal region of the human immunodeficiency virus type 1 gp41 ectodomain is important for Env-mediated fusion and virus infectivity. J. Virol., 1999, 73(3), 2469-2480.[http://dx.doi.org/10.1128/JVI.73.3.2469-2480.1999] [PMID: 9971832]
[24]
Pantophlet, R.; Wrin, T.; Cavacini, L.A.; Robinson, J.E.; Burton, D.R. Neutralizing activity of antibodies to the V3 loop region of HIV-1 gp120 relative to their epitope fine specificity. Virology, 2008, 381(2), 251-260.[http://dx.doi.org/10.1016/j.virol.2008.08.032] [PMID: 18822440]
[25]
Gazarian, K.G.; Palacios-Rodríguez, Y.; Gazarian, T.G.; Huerta, L. HIV-1 V3 loop crown epitope-focused mimotope selection by patient serum from random phage display libraries: Implications for the epitope structural features. Mol. Immunol., 2013, 54(2), 148-156.[http://dx.doi.org/10.1016/j.molimm.2012.11.016] [PMID: 23270686]
[26]
Muster, T.; Steindl, F.; Purtscher, M.; Trkola, A.; Klima, A.; Himmler, G.; Rüker, F.; Katinger, H. A conserved neutralizing epitope on gp41 of human immunodeficiency virus type 1. J. Virol., 1993, 67(11), 6642-6647.[http://dx.doi.org/10.1128/JVI.67.11.6642-6647.1993] [PMID: 7692082]
[27]
Purtscher, M.; Trkola, A.; Gruber, G.; Buchacher, A.; Predl, R.; Steindl, F.; Tauer, C.; Berger, R.; Barrett, N.; Jungbauer, A. A broadly neutralizing human monoclonal antibody against gp41 of human immunodeficiency virus type 1. AIDS Res. Hum. Retroviruses, 1994, 10(12), 1651-1658.[http://dx.doi.org/10.1089/aid.1994.10.1651] [PMID: 7888224]
[28]
Zwick, M.B.; Labrijn, A.F.; Wang, M.; Spenlehauer, C.; Saphire, E.O.; Binley, J.M.; Moore, J.P.; Stiegler, G.; Katinger, H.; Burton, D.R.; Parren, P.W. Broadly neutralizing antibodies targeted to the membrane-proximal external region of human immunodeficiency virus type 1 glycoprotein gp41. J. Virol., 2001, 75(22), 10892-10905.[http://dx.doi.org/10.1128/JVI.75.22.10892-10905.2001] [PMID: 11602729]
[29]
Reardon, P.N.; Sage, H.; Dennison, S.M.; Martin, J.W.; Donald, B.R.; Alam, S.M.; Haynes, B.F.; Spicer, L.D. Structure of an HIV-1-neutralizing antibody target, the lipid-bound gp41 envelope membrane proximal region trimer. Proc. Natl. Acad. Sci. USA, 2014, 111(4), 1391-1396.[http://dx.doi.org/10.1073/pnas.1309842111] [PMID: 24474763]
[30]
Gong, Z.; Kessans, S.A.; Song, L.; Dörner, K.; Lee, H.H.; Meador, L.R.; LaBaer, J.; Hogue, B.G.; Mor, T.S.; Fromme, P. Recombinant expression, purification, and biophysical characterization of the transmembrane and membrane proximal domains of HIV-1 gp41. Protein Sci., 2014, 23(11), 1607-1618.[http://dx.doi.org/10.1002/pro.2540] [PMID: 25155369]
[31]
Morris, M.C.; Depollier, J.; Mery, J.; Heitz, F.; Divita, G. A peptide carrier for the delivery of biologically active proteins into mammalian cells. Nat. Biotechnol., 2001, 19(12), 1173-1176.[http://dx.doi.org/10.1038/nbt1201-1173] [PMID: 11731788]
[32]
Lee, J.E.; Lim, H.J. LDP12, a novel cell-permeable peptide derived from L1 capsid protein of the human papillomavirus. Mol. Biol. Rep., 2012, 39(2), 1079-1086.[http://dx.doi.org/10.1007/s11033-011-0834-y] [PMID: 21573792]
[33]
Choi, J.M.; Ahn, M.H.; Chae, W.J.; Jung, Y.G.; Park, J.C.; Song, H.M.; Kim, Y.E.; Shin, J.A.; Park, C.S.; Park, J.W.; Park, T.K.; Lee, J.H.; Seo, B.F.; Kim, K.D.; Kim, E.S.; Lee, D.H.; Lee, S.K.; Lee, S.K. Intranasal delivery of the cytoplasmic domain of CTLA-4 using a novel protein transduction domain prevents allergic inflammation. Nat. Med., 2006, 12(5), 574-579.[http://dx.doi.org/10.1038/nm1385] [PMID: 16604087]
[34]
Bolhassani, A.; Jafarzade, B.S.; Mardani, G. In vitro and in vivo delivery of therapeutic proteins usingcell penetrating peptides. Pept, 2016, 16, 1-46.
[35]
Zhang, D.; Wang, J.; Xu, D. Cell-penetrating peptides as noninvasive transmembrane vectors for the development of novel multifunctional drug-delivery systems. J. Control. Release, 2016, 229, 130-139.[http://dx.doi.org/10.1016/j.jconrel.2016.03.020] [PMID: 26993425]
[36]
Bolhassani, A. Potential efficacy of cell-penetrating peptides for nucleic acid and drug delivery in cancer. Biochim. Biophys. Acta, 2011, 1816(2), 232-246.
[37]
Räägel, H.; Säälik, P.; Pooga, M. Peptide-mediated protein delivery-which pathways are penetrable? Biochim. Biophys. Acta, 2010, 1798(12), 2240-2248.[http://dx.doi.org/10.1016/j.bbamem.2010.02.013] [PMID: 20170627]
[38]
Rizzuti, M.; Nizzardo, M.; Zanetta, C.; Ramirez, A.; Corti, S. Therapeutic applications of the cell-penetrating HIV-1 Tat peptide. Drug Discov. Today, 2015, 20(1), 76-85.[http://dx.doi.org/10.1016/j.drudis.2014.09.017] [PMID: 25277319]
[39]
Vasconcelos, L.; Pärn, K.; Langel, U. Therapeutic potential of cell-penetrating peptides. Ther. Deliv., 2013, 4(5), 573-591.[http://dx.doi.org/10.4155/tde.13.22] [PMID: 23647276]
[40]
Muheem, A.; Shakeel, F.; Jahangir, M.A.; Anwar, M.; Mallick, N.; Jain, G.K.; Warsi, M.H.; Ahmad, F.J. A review on the strategies for oral delivery of proteins and peptides and their clinical perspectives. Saudi Pharm. J., 2016, 24(4), 413-428.[http://dx.doi.org/10.1016/j.jsps.2014.06.004] [PMID: 27330372]
[41]
Guo, Z.; Peng, H.; Kang, J.; Sun, D. Cell-penetrating peptides: Possible transduction mechanisms and therapeutic applications. Biomed. Rep., 2016, 4(5), 528-534.[http://dx.doi.org/10.3892/br.2016.639] [PMID: 27123243]
[42]
Sasagawa, T.; Pushko, P.; Steers, G.; Gschmeissner, S.E.; Hajibagheri, M.A.; Finch, J.; Crawford, L.; Tommasino, M. Synthesis and assembly of virus-like particles of human papillomaviruses type 6 and type 16 in fission yeast Schizosaccharomyces pombe. Virology, 1995, 206(1), 126-135.[http://dx.doi.org/10.1016/S0042-6822(95)80027-1] [PMID: 7831768]
[43]
Kwon, S.; Kwak, A.; Shin, H.; Choi, S.; Kim, S.; Lim, H.J. Application of a novel cell-permeable peptide-driven protein delivery in mouse blastocysts. Reproduction, 2013, 146(2), 145-153.[http://dx.doi.org/10.1530/REP-13-0203] [PMID: 23744616]
[44]
Rostami, B.; Irani, S.; Bolhassani, A.; Cohan, R.A. M918: A novel cell penetrating peptide for effective delivery of HIV-1 Nef and Hsp20-Nef proteins into eukaryotic cell lines. Curr. HIV Res., 2018, 16(4), 280-287.[http://dx.doi.org/10.2174/1570162X17666181206111859] [PMID: 30520377]
[45]
Tohidi, F.; Sadat, S.M.; Bolhassani, A.; Yaghobi, R. Construction and production of HIV-VLP harboring MPER-V3 for potential vaccine study. Curr. HIV Res., 2017, 15(6), 434-439.
[46]
Tohidi, F.; Sadat, S.M.; Bolhassani, A.; Yaghobi, R.; Larijani, M.S. Induction of a robust humoral response using HIV-1 VLPMPER-V3 as a novel candidate vaccine in BALB/c mice. Curr. HIV Res., 2019, 17(1), 33-41.[http://dx.doi.org/10.2174/1570162X17666190306124218] [PMID: 30843489]
[47]
Bolhassani, A.; Kardani, K.; Vahabpour, R.; Habibzadeh, N.; Aghasadeghi, M.R.; Sadat, S.M.; Agi, E. Prime/boost immunization with HIV-1 MPER-V3 fusion construct enhances humoral and cellular immune responses. Immunol. Lett., 2015, 168(2), 366-373.[http://dx.doi.org/10.1016/j.imlet.2015.10.012] [PMID: 26518142]
[48]
Jafarzade, B.S.; Sadat, S.M.; Yaghobi, R.; Bolhassani, A. Improving the potency of DNA vaccine encoding HIV-1 Nef antigen using two endogenous adjuvants in mouse model. Bratisl. Lek Listy, 2017, 118(9), 564-569.[http://dx.doi.org/10.4149/BLL_2017_108] [PMID: 29061065]
[49]
Sadat, S.M.; Zabihollahi, R.; Aghasadeghi, M.R.; Vahabpour, R.; Siadat, S.D.; Memarnejadian, A.; Azadmanesh, K.; Parivar, K. Application of SCR priming VLP boosting as a novel vaccination strategy against HIV-1. Curr. HIV Res., 2011, 9(3), 140-147.[http://dx.doi.org/10.2174/157016211795945223] [PMID: 21443517]
[50]
Elliott, G.; O’Hare, P. Intercellular trafficking and protein delivery by a herpesvirus structural protein. Cell, 1997, 88(2), 223-233.[http://dx.doi.org/10.1016/S0092-8674(00)81843-7] [PMID: 9008163]
[51]
Phelan, A.; Elliott, G.; O’Hare, P. Intercellular delivery of functional p53 by the herpesvirus protein VP22. Nat. Biotechnol., 1998, 16(5), 440-443.[http://dx.doi.org/10.1038/nbt0598-440] [PMID: 9592391]
[52]
Schwarze, S.R.; Dowdy, S.F. In vivo protein transduction: Intracellular delivery of biologically active proteins, compounds and DNA. Trends Pharmacol. Sci., 2000, 21(2), 45-48.[http://dx.doi.org/10.1016/S0165-6147(99)01429-7] [PMID: 10664605]
[53]
Schwarze, S.R.; Ho, A.; Vocero-Akbani, A.; Dowdy, S.F. In vivo protein transduction: Delivery of a biologically active protein into the mouse. Science, 1999, 285(5433), 1569-1572.[http://dx.doi.org/10.1126/science.285.5433.1569] [PMID: 10477521]
[54]
Wadia, J.S.; Dowdy, S.F. Protein transduction technology. Curr. Opin. Biotechnol., 2002, 13(1), 52-56.[http://dx.doi.org/10.1016/S0958-1669(02)00284-7] [PMID: 11849958]
[55]
Wadia, J.S.; Dowdy, S.F. Modulation of cellular function by TAT mediated transduction of full length proteins. Curr. Protein Pept. Sci., 2003, 4(2), 97-104.[http://dx.doi.org/10.2174/1389203033487289] [PMID: 12678849]
[56]
Zhang, M.X.; Li, Z.H.; Fang, Y.X.; Zhu, H.Z.; Xue, J.L.; Chen, J.Z.; Jia, W. TAT-phiC31 integrase mediates DNA recombination in mammalian cells. J. Biotechnol., 2009, 142(2), 107-113.[http://dx.doi.org/10.1016/j.jbiotec.2009.03.018] [PMID: 19439387]
[57]
Pan, C.; Lu, B.; Chen, H.; Bishop, C.E. Reprogramming human fibroblasts using HIV-1 TAT recombinant proteins OCT4, SOX2, KLF4 and c-MYC. Mol. Biol. Rep., 2010, 37(4), 2117-2124.[http://dx.doi.org/10.1007/s11033-009-9680-6] [PMID: 19669668]
[58]
Kameyama, S.; Horie, M.; Kikuchi, T.; Omura, T.; Tadokoro, A.; Takeuchi, T.; Nakase, I.; Sugiura, Y.; Futaki, S. Acid wash in determining cellular uptake of Fab/cell-permeating peptide conjugates. Biopolymers, 2007, 88(2), 98-107.[http://dx.doi.org/10.1002/bip.20689] [PMID: 17252560]
[59]
Motevalli, F.; Bolhassani, A.; Hesami, S.; Shahbazi, S. Supercharged green fluorescent protein delivers HPV16E7 DNA and protein into mammalian cells in vitro and in vivo. Immunol. Lett., 2018, 194, 29-39.[http://dx.doi.org/10.1016/j.imlet.2017.12.005] [PMID: 29273425]
[60]
Heitz, F.; Morris, M.C.; Divita, G. Twenty years of cell-penetrating peptides: From molecular mechanisms to therapeutics. Br. J. Pharmacol., 2009, 157(2), 195-206.[http://dx.doi.org/10.1111/j.1476-5381.2009.00057.x] [PMID: 19309362]
[61]
Munyendo, W.L.L.; Lv, H.; Benza-Ingoula, H.; Baraza, L.D.; Zhou, J. Cell penetrating peptides in the delivery of biopharmaceuticals. Biomolecules, 2012, 2(2), 187-202.[http://dx.doi.org/10.3390/biom2020187] [PMID: 24970133]
[62]
Kadkhodayan, S.; Jafarzade, B.S.; Sadat, S.M.; Motevalli, F.; Agi, E.; Bolhassani, A. Combination of cell penetrating peptides and heterologous DNA prime/protein boost strategy enhances immune responses against HIV-1 Nef antigen in BALB/c mouse model. Immunol. Lett., 2017, 188, 38-45.[http://dx.doi.org/10.1016/j.imlet.2017.06.003] [PMID: 28602843]
[63]
Kadkhodayan, S.; Bolhassani, A.; Sadat, S.M.; Irani, S.; Fotouhi, F. The efficiency of Tat cell penetrating peptide for intracellular uptake of HIV-1 Nef expressed in E. coli and mammalian cell. Curr. Drug Deliv., 2017, 14(4), 536-542.[http://dx.doi.org/10.2174/1567201813666161006114448] [PMID: 27719633]
[64]
Holm, T.; Räägel, H.; Andaloussi, S.E.L.; Hein, M.; Mäe, M.; Pooga, M.; Langel, Ü. Retro-inversion of certain cell-penetrating peptides causes severe cellular toxicity. Biochim. Biophys. Acta, 2011, 1808(6), 1544-1551.[http://dx.doi.org/10.1016/j.bbamem.2010.10.019] [PMID: 21070744]
[65]
Morris, M.C.; Heitz, A.; Mery, J.; Heitz, F.; Divita, G. An essential phosphorylation-site domain of human cdc25C interacts with both 14-3-3 and cyclins. J. Biol. Chem., 2000, 275(37), 28849-28857.[http://dx.doi.org/10.1074/jbc.M002942200] [PMID: 10864927]
[66]
Morris, M.C.; Robert-Hebmann, V.; Chaloin, L.; Mery, J.; Heitz, F.; Devaux, C.; Goody, R.S.; Divita, G. A new potent HIV-1 reverse transcriptase inhibitor. A synthetic peptide derived from the interface subunit domains. J. Biol. Chem., 1999, 274(35), 24941-24946.[http://dx.doi.org/10.1074/jbc.274.35.24941] [PMID: 10455170]
[67]
Alizadeh, S.; Irani, S.; Bolhassani, A.; Sadat, S.M. Simultaneous use of natural adjuvants and cell penetrating peptides improves HCV NS3 antigen-specific immune responses. Immunol. Lett., 2019, 212, 70-80.[http://dx.doi.org/10.1016/j.imlet.2019.06.011] [PMID: 31254535]
Related Journals
Current Protein & Peptide Science
Related Books
Frontiers in Protein and Peptide Sciences
Article Metrics
17