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Function: require_once
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Filename: controllers/Detail.php
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Line: 249
Function: _error_handler
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Filename: controllers/Detail.php
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Function: _error_handler
File: /var/www/html/index.php
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Filename: controllers/Detail.php
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Function: _error_handler
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Function: _error_handler
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Filename: models/Detail_model.php
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Function: insertAPISummary
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Advances in recombinant antibody technology and protein engineering have provided the opportunity to reduce antibodies to their smallest binding domain components and have concomitantly driven the requirement for devising strategies to increase serum half-life to optimise drug exposure, thereby increasing therapeutic efficacy. In this study, we adopted an immunization route to raise picomolar affinity shark immunoglobulin new antigen receptors (IgNARs) to target human serum albumin (HSA). From our model shark species, Squalus acanthias, a phage display library encompassing the variable binding domain of IgNAR (VNAR) was constructed, screened against target, and positive clones were characterized for affinity and specificity. N-terminal and C-terminal molecular fusions of our lead hit in complex with a naïve VNAR domain were expressed, purified and exhibited the retention of high affinity binding to HSA, but also cross-selectivity to mouse, rat and monkey serum albumin both in vitro and in vivo. Furthermore, the naïve VNAR had enhanced pharmacokinetic (PK) characteristics in both N- and C-terminal orientations and when tested as a three domain construct with naïve VNAR flanking the HSA binding domain at both the N and C termini. Molecules derived from this platform technology also demonstrated the potential for clinical utility by being available via the subcutaneous route of delivery. This study thus demonstrates the first in vivo functional efficacy of a VNAR binding domain with the ability to enhance PK properties and support delivery of multifunctional therapies.
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http://dx.doi.org/10.4161/mabs.22242 | DOI Listing |
Protein Sci
January 2025
Department of Biology, MIT, Cambridge, Massachusetts, USA.
Protein-protein interactions are often mediated by a modular peptide recognition domain binding to a short linear motif (SLiM) in the disordered region of another protein. To understand the features of SLiMs that are important for binding and to identify motif instances that are important for biological function, it is useful to examine the evolutionary conservation of motifs across homologous proteins. However, the intrinsically disordered regions (IDRs) in which SLiMs reside evolve rapidly.
View Article and Find Full Text PDFExpert Rev Vaccines
December 2024
Guangzhou Patronus Biotech Co, Ltd, Guangzhou, China.
Background: LYB001 is a recombinant protein COVID-19 vaccine displaying a receptor-binding domain (RBD) in a highly immunogenic array on virus-like particles (VLPs). This study assessed the immunogenicity and safety of LYB001 as a booster.
Research Design And Methods: In this randomized, active-controlled, double-blinded, phase 3 trial, participants aged ≥18 years received a booster with LYB001 or ZF2001 (Recombinant COVID-19 Vaccine).
iScience
December 2024
Center for Comparative Biomedicine, Ministry of Education Key Laboratory of Systems Biomedicine, State Key Laboratory of Medical Genomics, Institute of Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.
As an essential regulator of higher-order chromatin structures, CCCTC-binding factor (CTCF) is a highly conserved protein with a central DNA-binding domain of 11 tandem zinc fingers (ZFs), which are flanked by amino (N-) and carboxy (C-) terminal domains of intrinsically disordered regions. Here we report that CRISPR deletion of the entire C-terminal domain of alternating charge blocks decreases CTCF DNA binding but deletion of the C-terminal fragment of 116 amino acids results in increased CTCF DNA binding and aberrant gene regulation. Through a series of genetic targeting experiments, in conjunction with electrophoretic mobility shift assay (EMSA), circularized chromosome conformation capture (4C), qPCR, chromatin immunoprecipitation with sequencing (ChIP-seq), and assay for transposase-accessible chromatin with sequencing (ATAC-seq), we uncovered a negatively charged region (NCR) responsible for weakening CTCF DNA binding and chromatin accessibility.
View Article and Find Full Text PDFNAR Mol Med
October 2024
Division of Hematology, Department of Internal Medicine, Mayo Clinic, 200 1st St SW, Rochester, MN, USA.
The A1 domain in Von Willebrand Factor (VWF) initiates coagulation through binding to platelet glycoprotein GPIbα receptors. Von Willebrand Disease (VWD)-Mutations in A1 that either impair (type 2M) or enhance (type 2B) platelet adhesion to VWF can locally destabilize and even misfold the domain. We leveraged misfolding in the gain-of-function type 2B VWD phenotype as a target, distinct from the normal conformation.
View Article and Find Full Text PDFRSC Chem Biol
December 2024
School of Chemistry and Chemical Engineering, University of South China Hengyang 421001 China +86-743-8578079.
Androglobin (Adgb) was discovered as the fifth mammalian globin, but its structure and function remain elusive. In this study, the heme-binding globin domain of Adgb was expressed and its interaction with calmodulin (CaM) was investigated. The protein structure of Adgb and its complex with CaM were predicted using AlphaFold3 and HDOCK.
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