A5091497625- Monoclonal and Polyclonal Antibodies Research
- Porphyrin Metabolism and Disorders
- Biochemical and Molecular Research
- Methemoglobinemia and Tumor Lysis Syndrome
- Click Chemistry and Applications
- Protein Interaction Studies and Fluorescence Analysis
- Protein purification and stability
- RNA and protein synthesis mechanisms
- Gout, Hyperuricemia, Uric Acid
- Peptidase Inhibition and Analysis
- Hemoglobin structure and function
- DNA and Nucleic Acid Chemistry
- Chemical Synthesis and Analysis
- Salivary Gland Disorders and Functions
- Genomics and Phylogenetic Studies
- Bacteriophages and microbial interactions
- Fuel Cells and Related Materials
- Toxin Mechanisms and Immunotoxins
- Advanced biosensing and bioanalysis techniques
- Polymer Surface Interaction Studies
- Biotin and Related Studies
- RNA Interference and Gene Delivery
- Muscle and Compartmental Disorders
- Adenosine and Purinergic Signaling
- Liver Disease Diagnosis and Treatment
Gwangju Institute of Science and Technology
2016-2021
Government of the Republic of Korea
2018
Abstract Extension of the serum half-life is an important issue in developing new therapeutic proteins and expanding applications existing proteins. Conjugation fatty acid, a natural human albumin ligand, to protein/peptide was developed as technique extend vivo by taking advantages unusually long (HSA). However, for broad acid-conjugation, several issues should be addressed, including poor solubility acid substantial loss activity. Therefore, herein we systematically investigate conditions...
Polyethylene glycol (PEG) has been widely used as a serum half-life extender of therapeutic proteins. However, due to immune responses and low degradability PEG, developing alternatives PEG is required. Human albumin (HSA) several beneficial features extender, including very long half-life, good degradability, responses. In order further evaluate the efficacy HSA, we compared extent extension target protein, superfolder green fluorescent protein (sfGFP), upon HSA conjugation with...
Abstract Multistep cascade reactions in nature maximize reaction efficiency by co-assembling related enzymes. Such organization facilitates the processing of intermediates downstream Previously, studies on multienzyme nanocomplexes assembled DNA scaffolds demonstrated that closer interenzyme distance enhances overall efficiency. However, it remains unknown how active site orientation controlled at nanoscale can have an effect reaction. Here, we show alignment sites promotes By genetic...
Human serum albumin (HSA) has been investigated as a half-life extender of therapeutic proteins thanks to its unusually long half-life.
An inverse-electron-demand Diels–Alder (IEDDA) reaction using genetically encoded tetrazine variants enables rapid bioconjugation for diverse applications in vitro and cellulo. However, vivo is challenging, because the IEDDA coupling competes with elimination of partners vivo. Here, we tested hypothesis that a phenylalanine analogue containing hydrogen-substituted (frTet) would increase rate, thereby allowing successful We found rate superfolder green fluorescent protein (sfGFP) frTet...
Human serum albumin (HSA) has been used to extend the half-life of therapeutic proteins owing its exceptionally long via neonatal Fc receptor (FcRn)-mediated recycling mechanism. In most cases, only one HSA molecule was conjugated a protein, leading limited extension half-life. this study, we hypothesized that conjugation multiple molecules protein significantly further extends multivalent HSA-FcRn interactions. We chose urate oxidase (Uox), tetrameric for treatment gout, as model. previous...
Enzymes are biocatalysts that play key roles in diverse chemical reactions living organisms and industrial conversion processes generating value-added products. Since wild-type enzymes obtained from nature normally not optimal for various applications, enzyme engineering is usually required enhanced or new properties. Site-specific incorporation of a non-natural amino acid became powerful protein-engineering tool. In this short review, we briefly summarize our contribution to complex...
Abstract Mussel adhesive proteins (MAPs) have great potential as bioglues, particularly in wet conditions. Although vivo residue‐specific incorporation of 3,4‐dihydroxyphenylalanine (Dopa) tyrosine‐auxotrophic Escherichia coli cells allows for production Dopa‐incorporated bioengineered MAPs ( d MAPs), the low yield hinders practical application MAPs. This is due to translational activity a noncanonical amino acid, Dopa, E. cells. Herein, enhance MAPs, we investigated coexpression...
Urate oxidase derived from Aspergillus flavus has been investigated as a treatment for tumor lysis syndrome, hyperuricemia, and gout. However, its long-term use is limited owing to potential immunogenicity, low thermostability, short circulation time in vivo. Recently, urate isolated Arthrobacter globiformis (AgUox) reported be thermostable less immunogenic than the Aspergillus-derived oxidase. Conjugation of human serum albumin (HSA) therapeutic proteins become promising strategy prolong To...
Abstract Background Exogenously providing engineered Uox with enhanced half-life is one of the important urate-lowering treatments for gout. The potential PAT101, a recombinant human albumin (rHA)-conjugated variant, was evaluated and compared as novel gout treatment through various in vivo studies PAT101 competing drugs. Methods produced by site-specific conjugation rHA Aspergillus flavus ( Af Uox-rHA) clickable non-natural amino acid (frTet) Inverse electron demand Diels–Alder (IEDDA)...
3-arylpropiolonitriles (APN) are promising alternatives to maleimide for chemo-selective thiol conjugation, because the reaction product has a remarkably hydrolytic stability compared with that of thiol-maleimide reactions in vitro. However, whether cysteine modification APN enhances vivo remains unclear, probably due too short serum half-life protein observe significant cleavage thiol-maleimide/-APN products. The conjugation human albumin (HSA) therapeutic reportedly prolongs half-life. To...
Abstract Background: Exogenously providing engineered Uox with enhanced half-life is one of the important urate-lowering treatments for gout. The potential PAT101, a recombinant human albumin (rHA)-conjugated variant, was evaluated and compared as novel gout treatment through various in vivo studies PAT101 competing drugs. Methods: produced by site-specific conjugation rHA Aspergillus flavus ( Af Uox-rHA) clickable non-natural amino acid (frTet) Inverse electron demand Diels-Alder (IEDDA)...