Artificial chaperones based on thermoresponsive polymers recognize the unfolded state of the protein

Pavel Semenyuk, Tony Tiainen, Sami Hietala, Heikki Tenhu, Vladimir Aseyev, Vladimir Muronetz

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Stabilization of the enzymes under stress conditions is of special interest for modern biochemistry, bioengineering, as well as for formulation and target delivery of protein-based drugs. Aiming to achieve an efficient stabilization at elevated temperature with no influence on the enzyme under normal conditions, we studied chaperone-like activity of thermoresponsive polymers based on poly(dimethylaminoethyl methacrylate) (PDMAEMA) toward two different proteins, glyceraldehyde-3-phosphate dehydrogenase and chicken egg lysozyme. The polymers has been shown to do not interact with the folded protein at room temperature but form a complex upon heating to either protein unfolding or polymer phase transition temperature. A PDMAEMA-PEO block copolymer with a dodecyl end-group (d-PDMAEMA-PEO) as well as PDMAEMA-PEO without the dodecyl groups protected the denatured protein against aggregation in contrast to PDMAEMA homopolymer. No effect of the polymers on the enzymatic activity of the client protein was observed at room temperature. The polymers also partially protected the enzyme against inactivation at high temperature. The results provide a platform for creation of artificial chaperones with unfolded protein recognition which is a major feature of natural chaperones.
LanguageEnglish
JournalInternational Journal of Biological Macromolecules
Volume121
Pages536 - 545
ISSN0141-8130
DOIs
Publication statusPublished - 2019
MoE publication typeA1 Journal article-refereed

Fields of Science

  • Protein aggregation, Artificial chaperone, Protein stabilization, Thermoresponsive polymer, Protein-polyelectrolyte complexes, Poly(dimethylaminoethyl methacrylate)

Cite this

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title = "Artificial chaperones based on thermoresponsive polymers recognize the unfolded state of the protein",
abstract = "Stabilization of the enzymes under stress conditions is of special interest for modern biochemistry, bioengineering, as well as for formulation and target delivery of protein-based drugs. Aiming to achieve an efficient stabilization at elevated temperature with no influence on the enzyme under normal conditions, we studied chaperone-like activity of thermoresponsive polymers based on poly(dimethylaminoethyl methacrylate) (PDMAEMA) toward two different proteins, glyceraldehyde-3-phosphate dehydrogenase and chicken egg lysozyme. The polymers has been shown to do not interact with the folded protein at room temperature but form a complex upon heating to either protein unfolding or polymer phase transition temperature. A PDMAEMA-PEO block copolymer with a dodecyl end-group (d-PDMAEMA-PEO) as well as PDMAEMA-PEO without the dodecyl groups protected the denatured protein against aggregation in contrast to PDMAEMA homopolymer. No effect of the polymers on the enzymatic activity of the client protein was observed at room temperature. The polymers also partially protected the enzyme against inactivation at high temperature. The results provide a platform for creation of artificial chaperones with unfolded protein recognition which is a major feature of natural chaperones.",
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author = "Pavel Semenyuk and Tony Tiainen and Sami Hietala and Heikki Tenhu and Vladimir Aseyev and Vladimir Muronetz",
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Artificial chaperones based on thermoresponsive polymers recognize the unfolded state of the protein. / Semenyuk, Pavel; Tiainen, Tony; Hietala, Sami; Tenhu, Heikki; Aseyev, Vladimir; Muronetz, Vladimir.

In: International Journal of Biological Macromolecules, Vol. 121, 2019, p. 536 - 545.

Research output: Contribution to journalArticleScientificpeer-review

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T1 - Artificial chaperones based on thermoresponsive polymers recognize the unfolded state of the protein

AU - Semenyuk,Pavel

AU - Tiainen,Tony

AU - Hietala,Sami

AU - Tenhu,Heikki

AU - Aseyev,Vladimir

AU - Muronetz,Vladimir

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AB - Stabilization of the enzymes under stress conditions is of special interest for modern biochemistry, bioengineering, as well as for formulation and target delivery of protein-based drugs. Aiming to achieve an efficient stabilization at elevated temperature with no influence on the enzyme under normal conditions, we studied chaperone-like activity of thermoresponsive polymers based on poly(dimethylaminoethyl methacrylate) (PDMAEMA) toward two different proteins, glyceraldehyde-3-phosphate dehydrogenase and chicken egg lysozyme. The polymers has been shown to do not interact with the folded protein at room temperature but form a complex upon heating to either protein unfolding or polymer phase transition temperature. A PDMAEMA-PEO block copolymer with a dodecyl end-group (d-PDMAEMA-PEO) as well as PDMAEMA-PEO without the dodecyl groups protected the denatured protein against aggregation in contrast to PDMAEMA homopolymer. No effect of the polymers on the enzymatic activity of the client protein was observed at room temperature. The polymers also partially protected the enzyme against inactivation at high temperature. The results provide a platform for creation of artificial chaperones with unfolded protein recognition which is a major feature of natural chaperones.

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