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Biocompatible covalent reactive groups (CRGs) play pivotal roles in several areas of chemical biology and the life sciences, including targeted covalent inhibitor design and preparation of advanced biologic drugs, such as antibody-drug conjugates. In this study, we present the discovery that the small, chlorinated polyketide natural product cyclohelminthiol II (CHM-II) acts as a new type of cysteine/thiol-targeting CRG incorporating both reversible and irreversible reactivity. We devise the first syntheses of four simple cyclohelminthols, (±)-cyclohelminthol I-IV, with selective chlorinations (at C and C) and a Ni-catalyzed reductive cross coupling between an enone, a vinyl bromide and triethylsilyl chloride as the key steps.
View Article and Find Full Text PDFMultiplexing Label-Free Polymeric Nanocarriers via Antipolymer Antibodies.
ACS Sens
January 2025
Centre for Advanced Imaging (CAI) and Australian Institute for Bioengineering and Nanotechnology, ARC Training Centre for Innovation in Biomedical Imaging Technology, The University of Queensland, St. Lucia, Queensland 4072, Australia.
Recent examples of immune responses directed against the synthetic polymer poly(ethylene glycol) (PEG) have led to the development of biocompatible polymers, which are viewed as promising candidates to act as surrogate materials for use in biological applications, such as hydrophilic poly(2-oxazoline)s (POx). Despite this, the characterization of critical aspects of the immune response against these emerging materials is sparse, in part because no known monoclonal antibodies (mAbs) against this family of synthetic material have been reported. To advance the understanding of such responses, we report the successful isolation and characterization of hybridoma-derived mAbs with excellent specificity for different POx species and notable selectivity for highly branched polymer architectures over linear systems.
View Article and Find Full Text PDFEvaluation of ILAR and PRINTO classifications for juvenile idiopathic arthritis: oligoarticular JIA vs early-onset ANA-positive JIA.
Clin Rheumatol
January 2025
Department of Pediatric Rheumatology, Gazi University Faculty of Medicine, 06500, Besevler, Ankara, Turkey.
Objectives: The International League of Associations for Rheumatology (ILAR) juvenile idiopathic arthritis (JIA) classification was revisited by the Pediatric Rheumatology International Trials Organization (PRINTO) in 2018. Classifications should establish uniform groups to assist physicians in providing optimal care. Therefore, we evaluated changes proposed by PRINTO to highlight their impact on forming consistent groups regarding uveitis and treatment responses, particularly focusing on early-onset anti-nuclear antibody (ANA)-positive JIA.
View Article and Find Full Text PDFA simple and effective method to remove pigments from heterologous secretory proteins expressed in Pichia pastoris.
Adv Biotechnol (Singap)
February 2024
CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, 200030, China.
Pichia pastoris is a popular yeast host for high-level heterologous expression of proteins on an industrial scale owing to its reliable expression, robust growth, high fermentation density, and easy genetic manipulation and cultivation at a relatively low cost. Of particular interest is its high secretion efficiency for small proteins including insulin, human serum albumin, vaccines, enzymes, and llama-derived heavy-chain only antibodies (nanobodies) for pharmaceutical and research applications. However, a recurring challenge in using P.
View Article and Find Full Text PDFBiparatopic binding of ISB 1442 to CD38 in trans enables increased cell antibody density and increased avidity.
MAbs
December 2025
Ichnos Glenmark Innovation, New York, NY, USA.
ISB 1442 is a bispecific biparatopic antibody in clinical development to treat hematological malignancies. It consists of two adjacent anti-CD38 arms targeting non-overlapping epitopes that preferentially drive binding to tumor cells and a low-affinity anti-CD47 arm to enable avidity-induced blocking of proximal CD47 receptors. We previously reported the pharmacology of ISB 1442, designed to reestablish synthetic immunity in CD38+ hematological malignancies.
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