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Development of a novel DDS for site-specific PEGylated proteins

Because of the shifted focus in life science research from genome analyses to genetic and protein function analyses, we now know functions of numerous proteins. These analyses, including those of newly identified proteins, are expected to contribute to the identification of proteins of therapeutic v...

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Detalles Bibliográficos
Autores principales: Yoshioka, Yasuo, Tsunoda, Shin-ichi, Tsutsumi, Yasuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3113338/
https://www.ncbi.nlm.nih.gov/pubmed/21569400
http://dx.doi.org/10.1186/1752-153X-5-25
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author Yoshioka, Yasuo
Tsunoda, Shin-ichi
Tsutsumi, Yasuo
author_facet Yoshioka, Yasuo
Tsunoda, Shin-ichi
Tsutsumi, Yasuo
author_sort Yoshioka, Yasuo
collection PubMed
description Because of the shifted focus in life science research from genome analyses to genetic and protein function analyses, we now know functions of numerous proteins. These analyses, including those of newly identified proteins, are expected to contribute to the identification of proteins of therapeutic value in various diseases. Consequently, pharmacoproteomic-based drug discovery and development of protein therapies attracted a great deal of attention in recent years. Clinical applications of most of these proteins are, however, limited because of their unexpectedly low therapeutic effects, resulting from the proteolytic degradation in vivo followed by rapid removal from the circulatory system. Therefore, frequent administration of excessively high dose of a protein is required to observe its therapeutic effect in vivo. This often results in impaired homeostasis in vivo and leads to severe adverse effects. To overcome these problems, we have devised a method for chemical modification of proteins with polyethylene glycol (PEGylation) and other water-soluble polymers. In addition, we have established a method for creating functional mutant proteins (muteins) with desired properties, and developed a site-specific polymer-conjugation method to further improve their therapeutic potency. In this review, we are introducing our original protein-drug innovation system mentioned above.
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spelling pubmed-31133382011-06-14 Development of a novel DDS for site-specific PEGylated proteins Yoshioka, Yasuo Tsunoda, Shin-ichi Tsutsumi, Yasuo Chem Cent J Review Because of the shifted focus in life science research from genome analyses to genetic and protein function analyses, we now know functions of numerous proteins. These analyses, including those of newly identified proteins, are expected to contribute to the identification of proteins of therapeutic value in various diseases. Consequently, pharmacoproteomic-based drug discovery and development of protein therapies attracted a great deal of attention in recent years. Clinical applications of most of these proteins are, however, limited because of their unexpectedly low therapeutic effects, resulting from the proteolytic degradation in vivo followed by rapid removal from the circulatory system. Therefore, frequent administration of excessively high dose of a protein is required to observe its therapeutic effect in vivo. This often results in impaired homeostasis in vivo and leads to severe adverse effects. To overcome these problems, we have devised a method for chemical modification of proteins with polyethylene glycol (PEGylation) and other water-soluble polymers. In addition, we have established a method for creating functional mutant proteins (muteins) with desired properties, and developed a site-specific polymer-conjugation method to further improve their therapeutic potency. In this review, we are introducing our original protein-drug innovation system mentioned above. BioMed Central 2011-05-12 /pmc/articles/PMC3113338/ /pubmed/21569400 http://dx.doi.org/10.1186/1752-153X-5-25 Text en Copyright ©2011 Yoshioka et al
spellingShingle Review
Yoshioka, Yasuo
Tsunoda, Shin-ichi
Tsutsumi, Yasuo
Development of a novel DDS for site-specific PEGylated proteins
title Development of a novel DDS for site-specific PEGylated proteins
title_full Development of a novel DDS for site-specific PEGylated proteins
title_fullStr Development of a novel DDS for site-specific PEGylated proteins
title_full_unstemmed Development of a novel DDS for site-specific PEGylated proteins
title_short Development of a novel DDS for site-specific PEGylated proteins
title_sort development of a novel dds for site-specific pegylated proteins
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3113338/
https://www.ncbi.nlm.nih.gov/pubmed/21569400
http://dx.doi.org/10.1186/1752-153X-5-25
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