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A novel method for ...
A novel method for preparation of HAMLET-like protein complexes
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- Permyakov, Sergei E (författare)
- P.N. Lebedev Physical Institute of the Russian Academy of Sciences
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- Knyazeva, Ekaterina L (författare)
- P.N. Lebedev Physical Institute of the Russian Academy of Sciences
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- Leonteva, Marina V (författare)
- P.N. Lebedev Physical Institute of the Russian Academy of Sciences
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- Fadeev, Roman S (författare)
- P.N. Lebedev Physical Institute of the Russian Academy of Sciences
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- Chekanov, Aleksei V (författare)
- P.N. Lebedev Physical Institute of the Russian Academy of Sciences
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- Zhadan, Andrei P (författare)
- P.N. Lebedev Physical Institute of the Russian Academy of Sciences
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- Håkansson, Anders P (författare)
- Lund University,Lunds universitet,Experimentell infektionsmedicin, Malmö,Forskargrupper vid Lunds universitet,Experimental Infection Medicine, Malmö,Lund University Research Groups
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- Akatov, Vladimir S (författare)
- P.N. Lebedev Physical Institute of the Russian Academy of Sciences
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- Permyakov, Eugene A (författare)
- P.N. Lebedev Physical Institute of the Russian Academy of Sciences
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PN. Lebedev Physical Institute of the Russian Academy of Sciences Experimentell infektionsmedicin, Malmö (creator_code:org_t)
- Elsevier BV, 2011
- 2011
- Engelska 7 s.
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Ingår i: Biochimie. - : Elsevier BV. - 1638-6183 .- 0300-9084. ; 93:9, s. 501-1495
- Relaterad länk:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Some natural proteins induce tumor-selective apoptosis. α-Lactalbumin (α-LA), a milk calcium-binding protein, is converted into an antitumor form, called HAMLET/BAMLET, via partial unfolding and association with oleic acid (OA). Besides triggering multiple cell death mechanisms in tumor cells, HAMLET exhibits bactericidal activity against Streptococcus pneumoniae. The existing methods for preparation of active complexes of α-LA with OA employ neutral pH solutions, which greatly limit water solubility of OA. Therefore these methods suffer from low scalability and/or heterogeneity of the resulting α-LA - OA samples. In this study we present a novel method for preparation of α-LA - OA complexes using alkaline conditions that favor aqueous solubility of OA. The unbound OA is removed by precipitation under acidic conditions. The resulting sample, bLA-OA-45, bears 11 OA molecules and exhibits physico-chemical properties similar to those of BAMLET. Cytotoxic activities of bLA-OA-45 against human epidermoid larynx carcinoma and S. pneumoniae D39 cells are close to those of HAMLET. Treatment of S. pneumoniae with bLA-OA-45 or HAMLET induces depolarization and rupture of the membrane. The cells are markedly rescued from death upon pretreatment with an inhibitor of Ca(2+) transport. Hence, the activation mechanisms of S. pneumoniae death are analogous for these two complexes. The developed express method for preparation of active α-LA - OA complex is high-throughput and suited for development of other protein complexes with low-molecular-weight amphiphilic substances possessing valuable cytotoxic properties.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
Nyckelord
- Anti-Bacterial Agents
- Antineoplastic Agents
- Apoptosis
- Cell Death
- Cell Line, Tumor
- Humans
- Hydrogen-Ion Concentration
- Kinetics
- Lactalbumin
- Oleic Acid
- Oleic Acids
- Streptococcus pneumoniae
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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