| ○種別 (必須): | □ | 学術論文 (審査論文)
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| ○言語 (必須): | □ | 英語
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| ○招待 (推奨): |
| ○審査 (推奨): | □ | Peer Review
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| ○カテゴリ (推奨): | □ | 研究
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| ○学究種別 (推奨): |
| ○組織 (推奨): |
| ○著者 (必須): | 1. | (英) Hitoshi Ban (日) (読)
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| 2. | (英) Masanobu Nagano (日) (読)
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| 3. | (英) Julia Gavrilyuk (日) (読)
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| 4. | (英) Wataru Hakamata (日) (読)
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| 5. | 猪熊 翼 ([徳島大学.大学院医歯薬学研究部.薬学域.薬科学部門.創薬科学系.薬品製造化学])
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| 6. | (英) Carlos F Barbas III (日) (読)
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| ○題名 (必須): | □ | (英) Facile and Stabile Linkages through Tyrosine: Bioconjugation Strategies with the Tyrosine-Click Reaction (日)
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| ○要約 (任意): | □ | (英) The scope, chemoselectivity, and utility of the click-like tyrosine labeling reaction with 4-phenyl-3H-1,2,4-triazoline-3,5(4H)-diones (PTADs) is reported. To study the utility and chemoselectivity of PTAD derivatives in peptide and protein chemistry, we synthesized PTAD derivatives possessing azide, alkyne, and ketone groups and studied their reactions with amino acid derivatives and peptides of increasing complexity. With proteins we studied the compatibility of the tyrosine click reaction with cysteine and lysine-targeted labeling approaches and demonstrate that chemoselective trifunctionalization of proteins is readily achieved. In particular cases, we noted that PTAD decomposition resulted in formation of a putative isocyanate byproduct that was promiscuous in labeling. This side reaction product, however, was readily scavenged by the addition of a small amount of 2-amino-2-hydroxymethyl-propane-1,3-diol (Tris) to the reaction medium. To study the potential of the tyrosine click reaction to introduce poly(ethylene glycol) chains onto proteins (PEGylation), we demonstrate that this novel reagent provides for the selective PEGylation of chymotrypsinogen, whereas traditional succinimide-based PEGylation targeting lysine residues provided a more diverse range of PEGylated products. Finally, we applied the tyrosine click reaction to create a novel antibody-drug conjugate. For this purpose, we synthesized a PTAD derivative linked to the HIV entry inhibitor aplaviroc. Labeling of the antibody trastuzumab with this reagent provided a labeled antibody conjugate that demonstrated potent HIV-1 neutralization activity demonstrating the potential of this reaction in creating protein conjugates with small molecules. The tyrosine click linkage demonstrated stability to extremes of pH, temperature, and exposure to human blood plasma indicating that this linkage is significantly more robust than maleimide-type linkages that are commonly employed in bioconjugations. These studies support the broad utility of this reaction in the chemoselective modification of small molecules, peptides, and proteins under mild aqueous conditions over a broad pH range using a wide variety of biologically acceptable buffers such as phosphate buffered saline (PBS) and 2-amino-2-hydroxymethyl-propane-1,3-diol (Tris) buffers as well as others and mixed buffered compositions. (日)
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| ○キーワード (推奨): | 1. | (英) Click Chemistry (日) (読)
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| 2. | (英) Humans (日) (読)
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| 3. | (英) Hydrogen-Ion Concentration (日) (読)
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| 4. | (英) Models, Molecular (日) (読)
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| 5. | (英) Molecular Structure (日) (読)
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| 6. | (英) Polyethylene Glycols (日) (読)
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| 7. | (英) Temperature (日) (読)
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| 8. | (英) Triazoles (日) (読)
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| 9. | (英) Tyrosine (日) (読)
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| ○発行所 (推奨): |
| ○誌名 (必須): | □ | Bioconjugate Chemistry ([アメリカ化学会])
(pISSN: 1043-1802, eISSN: 1520-4812)
| ○ISSN (任意): | □ | 1520-4812
ISSN: 1043-1802
(pISSN: 1043-1802, eISSN: 1520-4812) Title: Bioconjugate chemistryTitle(ISO): Bioconjug ChemPublisher: American Chemical Society (NLM Catalog)
(Scopus)
(CrossRef)
(Scopus information is found. [need login]) | [継承] |
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| ○巻 (必須): | □ | 24
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| ○号 (必須): | □ | 4
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| ○頁 (必須): | □ | 520 532
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| ○都市 (任意): |
| ○年月日 (必須): | □ | 西暦 2013年 3月 27日 (平成 25年 3月 27日)
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| ○URL (任意): |
| ○DOI (任意): | □ | 10.1021/bc300665t (→Scopusで検索)
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| ○PMID (任意): | □ | 23534985 (→Scopusで検索)
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| ○Scopus (任意): | □ | 2-s2.0-84876470762
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| ○備考 (任意): | 1. | (英) Article.ELocationID: 10.1021/bc300665t (日)
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| 2. | (英) Article.PublicationTypeList.PublicationType: Journal Article (日)
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| 3. | (英) Article.PublicationTypeList.PublicationType: Research Support, N.I.H., Extramural (日)
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| 4. | (英) Article.PublicationTypeList.PublicationType: Research Support, Non-U.S. Gov't (日)
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| 5. | (英) OtherID: NIHMS461316 (日)
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| 6. | (英) OtherID: PMC3658467 (日)
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