Article
Chemistry, Multidisciplinary
Ya-Qiong Yan, Jia-Qi Wang, Lingze Zhang, Pei-Pei Yang, Xin-Wei Ye, Cong Liu, Da-Yong Hou, Wen-Jia Lai, Jie Wang, Xiang-Zhong Zeng, Wanhai Xu, Lei Wang
Summary: This article introduces an in vivo screening method of the OBOC library based on localized instillation beads, which is used to discover targeting peptides. By constructing a cavity inside a transplanted tumor of a mouse and injecting the OBOC heptapeptide library, three MDAMB-231 tumor-targeting peptides were discovered after an efficient elution process. The best peptide was verified to have 1.9-fold higher tumor accumulation than the commonly used targeting peptide RGD in vivo. Finally, two potential targeting proteins related to our targeting peptide were discovered. The in vivo LIB screening method expands the scope of OBOC peptide screening applications to discover targeting peptides feasibly and reliably.
Article
Chemistry, Organic
Antoine Blanc, Mihajlo Todorovic, Iulia Dude, Helen Merkens, Francois Benard, David M. Perrin
Summary: This study describes the solid-phase synthesis of a new somatostatin analog and explores its potential applications in the construction of one-bead-one-compound libraries. The synthesized analog was validated through fluorescent labeling and demonstrated binding to somatostatin receptor and staining of cancer cells. This research paves the way for the development of bioactive somatostatin analogs and peptide macrocycle libraries.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Immunology
Neil G. Rumachik, Stacy A. Malaker, Nicole K. Paulk
Summary: Advances in gene therapy product and process development have improved our understanding of the basic biology of recombinant AAV, with a particular focus on post-translational modifications of the capsid protein. Concerns about immunogenic responses to high doses of systemically administered rAAV have emphasized the importance of cataloging and tracking potentially immunogenic components of vector lots.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Chemistry, Organic
Bingjia Yan, Wenyi Li, Christian P. R. Hackenberger
Summary: This report introduces a novel building block for solid phase synthesis of beta-linked O-GlcNAcylated peptides, which carries acid labile silyl ether protecting groups. These protecting groups can be easily removed under TFA-mediated peptide cleavage conditions, leading to fewer synthetic steps and no intermediate purification compared to other protecting group strategies.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Biotechnology & Applied Microbiology
Minhyo Kang, Zening Wang, Xin Ge
Summary: This study focused on low-affinity Fc gamma receptors (Fc?Rs) IIA, IIB, and IIIA and successfully achieved correct post-translational modifications (PTMs) using human 293-F cells. The produced Fc?R ectodomains were fully biotinylated, N-glycosylated, had formed disulfide bond, and exhibited expected binding affinities. This one-step cell culture method for achieving multiple PTMs has applications for producing complex proteins of biomedical importance.
BIOTECHNOLOGY PROGRESS
(2023)
Article
Chemistry, Multidisciplinary
Mathias B. Danielsen, Niels Johan Christensen, Per T. Jorgensen, Knud J. Jensen, Jesper Wengel, Chenguang Lou
Summary: Cationic moieties attached to oligonucleotides increased binding affinity and stability, with the 2'-amino-LNA analogue carrying a triaminated linker showing the most pronounced effect. Molecular modeling revealed salt-bridge formation between positively charged polyamine moieties and the dsDNA targets, resulting in the observed triplex stabilization. All investigated monomers showed increased resistance against 3'-nucleolytic digestion.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Multidisciplinary
Senlian Hong, Chenhua Yu, Peng Wang, Yujie Shi, Weiqian Cao, Bo Cheng, Digantkumar G. Chapla, Yuanhui Ma, Jie Li, Emily Rodrigues, Yoshiki Narimatsu, John R. Yates, Xing Chen, Henrik Clausen, Kelly W. Moremen, Matthew Scott Macauley, James C. Paulson, Peng Wu
Summary: By modifying natural killer cells with glycan ligands targeting CD22, as well as selectins to promote trafficking to bone marrow, it is possible to achieve targeted killing of B lymphoma cells and improve cell trafficking to cancer cell locations, resulting in efficient suppression of lymphoma in vivo.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Kasper K. Sorensen, Narendra K. Mishra, Maciej P. Paprocki, Amit Mehrotra, Knud J. Jensen
Summary: The study investigated the use of high-performance reversed-phase flash chromatography (HPFC) for rapidly purifying laboratory-scale quantities of crude, synthetic peptides and chemically modified insulins, demonstrating its versatility for various types of peptides. Depending on the peptide's purity profile, HPFC can serve as a standalone purification method or as a pre-purification step before final HPLC purification, providing guidelines for synthetic peptides and small proteins. HPFC is considered a valuable alternative to HPLC purification for peptides and small proteins.
Article
Chemistry, Multidisciplinary
Karin Mannerstedt, Narendra Kumar Mishra, Ebbe Engholm, Morten Lundh, Charlotte S. Madsen, Philip J. Pedersen, Priska Le-Huu, Soren L. Pedersen, Nina Buch-Manson, Bjorn Borgstrom, Thomas Brimert, Lisbeth N. Fink, Keld Fosgerau, Niels Vrang, Knud J. Jensen
Summary: A glucose responsive insulin (GRI) has been developed using glucose cleavable linkers based on hydrazone and thiazolidine structures, demonstrating glucose responsiveness in vitro, particularly for thiazolidines. Clamp studies confirmed increased glucose infusion at hyperglycemic conditions for one GRI, indicating a true glucose response. The glucose responsive cleavable linker in these GRIs drives the release of active insulin from a circulating depot in response to changes in glucose levels.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Multidisciplinary
Thomas Holmstrom, Mette Galsgaard Malle, Shunliang Wu, Knud Jorgen Jensen, Nikos S. Hatzakis, Christian Marcus Pedersen
Summary: This paper introduces a new lipid that can change its conformation based on the presence of Zn2+, triggered by the metal chelator Na(2)EDTA. The lipid was successfully incorporated into stable liposomes and showed potential for releasing the fluorescent cargo through a conformational change.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Thomas Norberg, Elisabet Kallin, Ola Blixt
Summary: A simple method for attaching and detaching carbobenzyloxy (Cbz) groups at the reducing end of sugars was developed, facilitating the efficient preparation of specific oligosaccharide structures.
CARBOHYDRATE RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Felix Tobola, Martin Lepsik, Syeda Rehana Zia, Hakon Leffler, Ulf J. Nilsson, Ola Blixt, Anne Imberty, Birgit Wiltschi
Summary: This study introduced non-canonical tryptophan analogues into the ligand binding site of Galectin-1 and found two variants with reduced affinity for certain sugars. Through fluorescence polarization competition assay and molecular modeling, the researchers provided structural clues for the changes in affinity.
Article
Chemistry, Multidisciplinary
Christian Kofoed, Shunliang Wu, Kasper K. Sorensen, Tuule Treiberg, Johnny Arnsdorf, Sara P. Bjorn, Tanja L. Jensen, Bjorn G. Voldborg, Mikkel B. Thygesen, Knud J. Jensen, Sanne Schoffelen
Summary: Chemical modification of proteins is important but challenging to achieve high selectivity on lysine amino groups. Researchers have recently developed a highly selective acylation method using a new tag sequence called Lys-His, which enables mild and selective acylation of lysine amino groups. This method provides flexibility in modification site by inserting the tag at the C-terminus or in loops of proteins.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Gokce Engudar, Cristina Rodriguez-Rodriguez, Narenda Kumar Mishra, Marta Bergamo, Guillaume J. Amouroux, Knud J. Jensen, Katayoun O. Saatchi, Urs O. Hafeli
Summary: This study found that the pharmacokinetics of insulin can be directly controlled with metal ions after covalent attachment of specific abiotic ligands. This provides new insights for exploring novel drug delivery strategies.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Biochemistry & Molecular Biology
Thomas Lund Koch, Iris Bea L. Ramiro, Paula Florez Salcedo, Ebbe Engholm, Knud Jorgen Jensen, Kevin Chase, Baldomero M. Olivera, Walden Emil Bjorn-Yoshimoto, Helena Safavi-Hemami
Summary: Somatostatin and its related peptides (SSRPs) are a family of hormones that play important roles in vertebrates and invertebrates. Recent discovery of SSRP-like toxins in venomous cone snails suggests the presence of a related signaling system in mollusks and potentially other protostomes. By identifying and studying the genes involved in this signaling system, it has been found that SSRP-like peptides are present in various animal phyla, challenging the prevailing hypothesis about their evolutionary relationship. Additionally, the study shows that the genes associated with venom experience rapid directional selection to target receptors in prey.
MOLECULAR BIOLOGY AND EVOLUTION
(2022)
Article
Biochemistry & Molecular Biology
Knud J. Jensen, Mikkel B. Thygesen, Kasper K. Sorensen, Shunliang Wu, Tuule Treiberg, Sanne Schoffelen
Summary: The chemical modification of proteins plays a crucial role in chemical biology, biotechnology, and the production of modified biopharmaceuticals. Two methods using poly-His sequences have been developed for directing selective acylation of proteins at the N-terminus or specific Lys residue. These methods offer high selectivity and maintain the capacity for immobilized metal ion affinity chromatography.
Article
Biochemical Research Methods
Shunliang Wu, Mads Ostergaard, Freja Fredholt, Niels Johan Christensen, Kasper K. Sorensen, Narendra K. Mishra, Hanne M. Nielsen, Knud J. Jensen
Summary: Chemical modification of peptides and proteins, such as PEGylation and lipidation, can create new conjugates with different properties. However, these conjugates are often not responsive to stimuli. This study reports the Ca2+-responsive properties of conjugates of oligogalacturonic acids (OGAs), derived from plant pectin. The self-assembly of OGA conjugates was studied and found to depend on OGA sequence length, as well as Zn2+ and Ca2+ concentrations.
BIOCONJUGATE CHEMISTRY
(2023)
Article
Biology
Freja Bohr, Soren S. -R. Bohr, Narendra Kumar Mishra, Nicolas Sebastian Gonzalez-Foutel, Henrik Dahl Pinholt, Shunliang Wu, Emilie Milan Nielsen, Min Zhang, Magnus Kjaergaard, Knud J. Jensen, Nikos S. Hatzakis
Summary: Single-molecule studies reveal the pathway organization of insulin hexamers' self-assembly and disassembly, and how this is remodeled by regulatory cues and formulations. The abundance and kinetics of all oligomeric species are assessed. Insulin formulations with diverse oligomerization states play a crucial role in diabetes treatment interventions.
COMMUNICATIONS BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Vanessa Ruck, Narendra K. Mishra, Kasper K. Sorensen, Mikkel B. Liisberg, Ane B. Sloth, Cecilia Cerretani, Christian B. Mollerup, Andreas Kjaer, Chenguang Lou, Knud J. Jensen, Tom Vosch
Summary: DNA-stabilized silver nanoclusters (DNA-AgNCs) have biocompatibility and intriguing properties but lack of structural information and predictable conjugation strategies hinder their bioimaging applications. A copper-free click chemistry method is introduced to link well-characterized DNA-AgNCs to molecules of interest. The conjugation is confirmed through MS, HPLC, and time-resolved anisotropy measurements. DNA-AgNCs show unaffected spectroscopic properties after linking reactions. Fluorescence imaging studies on CHO cells overexpressing human insulin receptor B (hIR-B) demonstrate the specific staining of cell membranes, indicating that DNA-AgNCs are promising candidates for bioimaging applications with an easily implementable linking strategy when the DNA-AgNC structure is known.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Letter
Microbiology
Vera Kuzina Poulsen, Elahe Ghanei Moghadam, Stjepan Kresimir Kracun, Birgit Albrecht Svendsen, Wioleta Marta Nielsen, Gunnar Oregaard, Anders Krarup
Summary: By high-throughput screening of 1232 Lactococcus lactis strains, it was found that most strains with texturing abilities in fermented milk were also capable of enhancing the texture in fermented soybean matrices. The production of exocellular polysaccharides is believed to contribute positively to the improved texture in both milk and plant-based fermentation.
FEMS MICROBIOLOGY LETTERS
(2022)