ArticleJournal of controlled release : official journal of the Controlled Release Society2013
Site-specific fatty acid-conjugation to prolong protein half-life in vivo.
Article in Journal of controlled release : official journal of the Controlled Release Society, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
20 citing papers in PubMed, 52 citations in OpenAlex.
- Artificial lipidation of proteins and peptides: from mechanism to clinical applications.The FEBS journal · 2026Review
- Article
- Orthogonal Translation for Site-Specific Installation of Post-translational Modifications.Chemical reviews · 2024Review
- Site-selective fatty acid chain conjugation of the N-terminus of the recombinant human granulocyte colony-stimulating factor.Frontiers in bioengineering and biotechnology · 2024Article
- Enhancing Anticancer Efficacy of Chemotherapeutics Using Targeting Ligand-Functionalized Synthetic Antigen Receptor-Mesenchymal Stem Cells.Pharmaceutics · 2023Article
- Functional analysis of protein post-translational modifications using genetic codon expansion.Protein science : a publication of the Protein Society · 2023Review
- Doxorubicin-Based Hybrid Compounds as Potential Anticancer Agents: A Review.Molecules (Basel, Switzerland) · 2022Review
- Tuning protein half-life in mouse using sequence-defined biopolymers functionalized with lipids.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- 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
- Applications of DNA-Functionalized Proteins.International journal of molecular sciences · 2021Review
- Site-Specific Lipidation of a Small-Sized Protein Binder Enhances the Antitumor Activity through Extended Blood Half-Life.ACS omega · 2020Article
- Nanotechnology as a Platform for the Development of Injectable Parenteral Formulations: A Comprehensive Review of the Know-Hows and State of the Art.Pharmaceutics · 2020Review
- The Minimal Effect of Linker Length for Fatty Acid Conjugation to a Small Protein on the Serum Half-Life Extension.Biomedicines · 2020Article
- Recombinant Peptide Production Platform Coupled with Site-Specific Albumin Conjugation Enables a Convenient Production of Long-Acting Therapeutic Peptide.Pharmaceutics · 2020Article
- Practical Considerations, Challenges, and Limitations of Bioconjugation via Azide-Alkyne Cycloaddition.Bioconjugate chemistry · 2018Review
- Generation of therapeutic protein variants with the human serum albumin binding capacity via site-specific fatty acid conjugation.Scientific reports · 2017Article
- Site-specific albumination of a therapeutic protein with multi-subunit to prolong activity in vivo.Journal of controlled release : official journal of the Controlled Release Society · 2015Article
- Site-specific bioconjugation of an organometallic electron mediator to an enzyme with retained photocatalytic cofactor regenerating capacity and enzymatic activity.Molecules (Basel, Switzerland) · 2015Article
- Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
Therapeutic proteins are indispensable in treating numerous human diseases. However, therapeutic proteins often suffer short serum half-life. In order to extend the serum half-life, a natural albumin ligand (a fatty acid) has been conjugated to small therapeutic peptides resulting in a prolonged serum half-life via binding to patients' serum albumin in vivo. However, fatty acid-conjugation has limited applicability due to lack of site-specificity resulting in the heterogeneity of conjugated proteins and a significant loss in pharmaceutical activity. In order to address these issues, we exploited the site-specific fatty acid-conjugation to a permissive site of a protein, using copper-catalyzed alkyne-azide cycloaddition, by linking a fatty acid derivative to p-ethynylphenylalanine incorporated into a protein using an engineered pair of yeast tRNA/aminoacyl tRNA synthetase. As a proof-of-concept, we show that single palmitic acid conjugated to superfolder green fluorescent protein (sfGFP) in a site-specific manner enhanced a protein's albumin-binding in vitro about 20 times and the serum half-life in vivo 5 times when compared to those of the unmodified sfGFP. Furthermore, the fatty acid conjugation did not cause a significant reduction in the fluorescence of sfGFP. Therefore, these results clearly indicate that the site-specific fatty acid-conjugation is a very promising strategy to prolong protein serum half-life in vivo without compromising its folded structure and activity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.