ArticleScientific reports2017
Generation of therapeutic protein variants with the human serum albumin binding capacity via site-specific fatty acid conjugation.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 40 citations in OpenAlex.
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- Fibroblast activation protein targeting radiopharmaceuticals: From drug design to clinical translation.Acta pharmaceutica Sinica. B · 2025Review
- Lipid Metabolism and Immune Function: Chemical Tools for Insights into T-Cell Biology.Chembiochem : a European journal of chemical biology · 2025Review
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- Engineering of Recombinant Human Papillomavirus 16 L1 Protein for Incorporation withJournal of microbiology and biotechnology · 2024Article
- Orthogonal Translation for Site-Specific Installation of Post-translational Modifications.Chemical reviews · 2024Review
- Functional analysis of protein post-translational modifications using genetic codon expansion.Protein science : a publication of the Protein Society · 2023Review
- Preparation and Characterization of Site-Specific Fatty Chain-Modified Recombinant Human Granulocyte Colony Stimulating Factor.Frontiers in bioengineering and biotechnology · 2022Article
- Chemical approaches for investigating site-specific protein S-fatty acylation.Current opinion in chemical biology · 2021Review
- Site-Specific Lipidation of a Small-Sized Protein Binder Enhances the Antitumor Activity through Extended Blood Half-Life.ACS omega · 2020Article
- The Minimal Effect of Linker Length for Fatty Acid Conjugation to a Small Protein on the Serum Half-Life Extension.Biomedicines · 2020Article
- A recent update on the use of microbial transglutaminase for the generation of biotherapeutics.World journal of microbiology & biotechnology · 2020Review
- Extracellular vesicles in the tumor microenvironment: old stories, but new tales.Molecular cancer · 2019Review
- A Peptide-Based HIV-1 Fusion Inhibitor with Two Tail-Anchors and Palmitic Acid Exhibits Substantially Improved In Vitro and Ex Vivo Anti-HIV-1 Activity and Prolonged In Vivo Half-Life.Molecules (Basel, Switzerland) · 2019Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Extension of the serum half-life is an important issue in developing new therapeutic proteins and expanding applications of existing therapeutic proteins. Conjugation of fatty acid, a natural human serum albumin ligand, to a therapeutic protein/peptide was developed as a technique to extend the serum half-life in vivo by taking advantages of unusually long serum half-life of human serum albumin (HSA). However, for broad applications of fatty acid-conjugation, several issues should be addressed, including a poor solubility of fatty acid and a substantial loss in the therapeutic activity. Therefore, herein we systematically investigate the conditions and components in conjugation of fatty acid to a therapeutic protein resulting in the HSA binding capacity without compromising therapeutic activities. By examining the crystal structure and performing dye conjugation assay, two sites (W160 and D112) of urate oxidase (Uox), a model therapeutic protein, were selected as sites for fatty acid-conjugation. Combination of site-specific incorporation of a clickable p-azido-L-phenylalanine to Uox and strain-promoted azide-alkyne cycloaddition allowed the conjugation of fatty acid (palmitic acid analog) to Uox with the HSA binding capacity and retained enzyme activity. Deoxycholic acid, a strong detergent, greatly enhanced the conjugation yield likely due to the enhanced solubility of palmitic acid analog.
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