Article
Biochemical Research Methods
Luis A. Prieto-Costas, Genesis R. Rivera-Cordero, Jose M. Rivera
Summary: The study developed a flow cytometry-based method to quantify protein encapsulation and track changes in colloidal particles. The hydrophobicity of the particles was found to be the dominant factor in enhancing protein affinity. Confocal laser scanning microscopy (CLSM) imaging provided additional information about protein distribution and the impact of ligands on binding. The study also tested the feasibility of tuning the affinity of particles with a biotin ligand and found that increasing the amount of ligand initially enhanced binding, but led to saturation due to noncovalent cross-linking. The strategy offers advantages for high-throughput analysis and may have implications for drug delivery applications.
BIOCONJUGATE CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Sijie Xian, Yuanhui Xiang, Dongping Liu, Bowen Fan, Katarina Mitrova, Rachel C. Ollier, Bo Su, Muhammad Ali Alloosh, Jiri Jiracek, Michael Sturek, Mouhamad Alloosh, Matthew J. Webber
Summary: A nanoscale complex combining electrostatic- and dynamic-covalent interactions between a synthetic dendrimer carrier and a modified insulin analogue has been developed, providing an injectable insulin depot with glucose-responsive and long-lasting insulin availability.
ADVANCED MATERIALS
(2023)
Article
Engineering, Biomedical
Paige N. Smith, Leran Mao, Kaustubh Sinha, Alan J. Russell
Summary: Organophosphate nerve agents (OPNAs) are extremely toxic chemical warfare agents. Access to prophylactic measures is crucial due to their toxicity. Researchers have developed an enhanced delivery system by engineering butyrylcholinesterase (BChE) to the surface of red blood cells (RBCs).
ACTA BIOMATERIALIA
(2021)
Article
Polymer Science
Sharareh Zeynalzadeh, Elham Dehghani, Ayla Hassani, Ali Baradar Khoshfetrat, Mehdi Salami-Kalajahi
Summary: The goal of this study was to synthesize and evaluate the structural and anti-cancer properties of the poly(amidoamine)-curcumin dendrimer complex. The results showed that the modified curcumin was effectively released and exhibited better inhibitory effect on tumor cell growth. This suggests the potential of the poly(amidoamine) dendrimer derivative for cancer treatments.
Article
Chemistry, Multidisciplinary
Zhen Xu, Tianhui Shi, Fengye Mo, Wenqian Yu, Yu Shen, Qunying Jiang, Fuan Wang, Xiaoqing Liu
Summary: In this study, programmable DNA-protein superstructures were successfully assembled through biomimetic assembly, by combining programmable polymer DNA wire with alkaline protein protamine to form densely packed DNA nanospheres. These DNA-protein superstructures exhibited specifically high affinity and stability, enabling high cancer cell selectivity and reduced side effects.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Review
Chemistry, Multidisciplinary
Alireza Poustforoosh, Mohammad Hadi Nematollahi, Hassan Hashemipour, Abbas Pardakhty
Summary: This review discusses the challenges and barriers in drug delivery to the brain, as well as strategies and pathways to overcome the blood-brain barrier. The application of bioconjugated vesicles as nanocarriers for enhancing drug loading into the brain is emphasized.
JOURNAL OF CONTROLLED RELEASE
(2022)
Review
Pharmacology & Pharmacy
Chen Chen, Yuqi Zhang, Zhaowei Chen, Huanghao Yang, Zhen Gu
Summary: Using natural cells as drug carriers has become a hot topic in recent years due to their biocompatibility and dynamic properties. Instead of focusing on what cells display, attention is now shifting towards how cells change, including surface protein patterns, morphologies, and in-situ generation of therapeutics, to develop advanced drug delivery systems.
ADVANCED DRUG DELIVERY REVIEWS
(2021)
Review
Instruments & Instrumentation
Avijit Kumar Bakshi, Tanweer Haider, Rahul Tiwari, Vandana Soni
Summary: This article discusses the crucial role of multivalency in biochemical interactions and highlights the challenges and recent advances in designing and developing multivalent nanoconstructs for drug delivery.
DRUG DELIVERY AND TRANSLATIONAL RESEARCH
(2022)
Article
Medicine, Research & Experimental
Aida Falgas, Annabel Garcia-Leon, Yaiza Nunez, Naroa Serna, Laura Sanchez-Garcia, Ugutz Unzueta, Eric Volta-Duran, Marc Arago, Patricia Alamo, Lorena Alba-Castellon, Jorge Sierra, Alberto Gallardo, Antonio Villaverde, Esther Vazquez, Ramon Mangues, Isolda Casanova
Summary: Due to the high toxicity of immunotoxins, developing new therapies for DLBCL patients is urgently needed. This study demonstrated that the polypeptidic nanoparticle T22-DITOX-H6, which specifically targeted CXCR4(+) DLBCL cells, showed high cytotoxicity without adverse effects. It could potentially provide a new strategy for selectively eliminating DLBCL cells.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Chemistry, Multidisciplinary
Alexis Eras, Danna Castillo, Margarita Suarez, Nelson Santiago Vispo, Fernando Albericio, Hortensia Rodriguez
Summary: DDS technology aims to improve the effectiveness of cancer treatment and reduce side effects. Erythrocytes, antibodies, and nanoparticles can be used as drug carriers. Antibody-drug conjugates involving covalent linkage have shown promise as a cancer treatment.
FRONTIERS IN CHEMISTRY
(2022)
Article
Polymer Science
Meshal Alshamrani
Summary: This article discusses the application of nanomaterials in the field of medicine, focusing on the crucial role of nanoparticles in drug therapy. The article introduces different types of nanoparticles and their conjugation with biomolecules, and explores the application areas of nanomaterials in disease diagnosis and treatment, including bio-imaging, drug delivery, biosensing, and tissue engineering.
Article
Chemistry, Multidisciplinary
Soumya Jyoti Singha Roy, Conor Loynd, Delilah Jewel, Sarah E. Canarelli, Elise D. Ficaretta, Quan A. Pham, Eranthie Weerapana, Abhishek Chatterjee
Summary: We have developed a novel visible-light-catalyzed bioconjugation reaction, PhotoCLIC, for selective modification of 5-hydroxytryptophan residue (5HTP) on full-length proteins. This reaction enables rapid and site-specific protein bioconjugation using catalytic amounts of methylene blue and blue/red light-emitting diodes. The PhotoCLIC product has a unique structure likely formed through singlet oxygen-dependent modification of 5HTP. PhotoCLIC has a wide substrate scope and is compatible with strain-promoted azide-alkyne click reaction, allowing for site-specific dual-labeling of a target protein.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Faisal K. Algethami, Ilyes Saidi, Hichem Ben Jannet, M. Khairy, Babiker Y. Abdulkhair, Youssef O. Al-Ghamdi, Hani Nasser Abdelhamid
Summary: Cadmium sulfide quantum dots were successfully embedded into chitosan using an in situ hydrothermal method. The resulting CdS@CTS quantum dots showed high selectivity towards copper ions and can be used for naked-eye detection of heavy metals.
Article
Chemistry, Multidisciplinary
Lea N. C. Rochet, Calise Bahou, Jonathan P. Wojciechowski, Ilias Koutsopetras, Phyllida Britton, Richard J. Spears, Ioanna A. Thanasi, Baihao Shao, Lisha Zhong, Dejan-Kresimir Bucar, Abil E. Aliev, Michael J. Porter, Molly M. Stevens, James R. Baker, Vijay Chudasama
Summary: This study demonstrates the potential of pyridazinediones as novel reversible and tuneable covalent cysteine modifiers. The electrophilicity of pyridazinediones correlates to the rates of the Michael addition and retro-Michael deconjugation reactions, making them an enticing platform for readily tuneable and reversible thiol addition/release. The regioselectivity of the reaction is explored and the increased reactivity of aryl bearing pyridazinediones is explained using DFT calculations and corroborating findings with SCXRD. Application of this fundamental discovery is also demonstrated in the development of more rapid disulfide rebridging agents.
Review
Chemistry, Multidisciplinary
Diana Morzy, Maartje Bastings
Summary: The mobility of coupled receptors plays a crucial role in multivalent processes, affecting receptor recruitment, local accumulation, complex formation, and lipid environment.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Anselm F. L. Schneider, Marina Kithil, M. Cristina Cardoso, Martin Lehmann, Christian P. R. Hackenberger
Summary: The challenge of delivering proteins into cells has been addressed by conjugating arginine-rich cell-penetrating peptides to the cell surface, enabling efficient delivery of protein-CPP conjugates. The use of thiol-reactive cell-penetrating peptides allows for simple co-incubation to deliver thiol-containing proteins, greatly simplifying protein and antibody delivery with minimal genetic or chemical engineering.
Article
Chemistry, Multidisciplinary
Anselm F. L. Schneider, Laila S. Benz, Martin Lehmann, Christian P. R. Hackenberger
Summary: Super-resolution microscopy in living cells can be enhanced by the use of engineered cell-permeable and highly fluorescent nanobodies as intracellular targeting agents. These semi-synthetic nanobodies, with bright fluorescent signals achieved through intramolecular photostabilization, have a cleavable cell-penetrating peptide for efficient cellular entry. Their utility has been demonstrated in functional analysis through monitoring cell division and DNA replication via confocal and STED microscopy.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Christian E. Stieger, Luise Franz, Frieder Koerlin, Christian P. R. Hackenberger
Summary: Diethynyl phosphinates are developed as bisfunctional electrophiles for site-selective modification of peptides, proteins, and antibodies. The obtained conjugates are stable in human plasma and in the presence of small thiols. This method is suitable for generating functional protein conjugates, including homogeneously rebridged antibodies that remain specific for their target.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Organic
Marc-Andre Kasper, Lukas Lassak, Annette M. Vogl, Isabelle Mai, Jonas Helma, Dominik Schumacher, Christian P. R. Hackenberger
Summary: Bis-ethynylphosphonamidates allow for a simple chemoselective addition of two thiol-containing modules in a row. Functional O-substituents with tunable hydrophilicity enable further subsequent conjugations, facilitating the construction of protein-protein conjugates. The increased spacer length between the ethynylphosphonamidates simplifies the formation of a conjugate from bulky proteins.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Carolina Sarto, Sebastian Florez-Rueda, Mehrnoosh Arrar, Christian P. R. Hackenberger, Daniel Lauster, Santiago Di Lella
Summary: This study determined the binding affinity between ACE2-derived peptides and the RBD of SARS-CoV-2, and identified critical peptide anchors. New ACE2-derived peptides were developed based on interface analysis, and a correlation between helicity and binding affinity was found. Additionally, a cyclized version of p6 with increased helicity and reduced K (D) value was created.
BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemical Research Methods
Lutz Adam, Eva Muller, Kai Ludwig, Simon Klenk, Daniel Lauster, Susanne Liese, Andreas Herrmann, Christian P. R. Hackenberger
Summary: The conjugation of virus-binding ligands to multivalent carriers is an effective strategy to inhibit viral entry into host cells. Even partially sialylated ligands can retain their inhibitory effect, and carriers carrying two different ligand-linker structures showed higher viral inhibition.
BIOCONJUGATE CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Pascal M. Engelhardt, Sebastian Florez-Rueda, Marco Drexelius, Joerg-Martin Neudoerfl, Daniel Lauster, Christian P. R. Hackenberger, Ronald Kuehne, Ines Neundorf, Hans-Guenther Schmalz
Summary: Researchers used a rigidified diproline-derived module ProM-5 to induce alpha helicity in ACE2-inspired peptide sequences. They found increased alpha helicity when non-binding amino acids were replaced with alanine. The binding affinities of the peptides towards the spike protein showed that the alpha-helical content had only a subtle influence, with one specific peptide displaying a strong binding affinity.
Article
Chemistry, Multidisciplinary
Abhishek Saha, Shaswati Mandal, Jan Vincent V. Arafiles, Jacobo Gomez-Gonzalez, Christian P. R. Hackenberger, Ashraf Brik
Summary: By studying DABCYL-modified cR10 peptides and their derivatives, it was found that the efficiency of Ub cargo entering living cells can be significantly improved, which is of great research value.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Review
Chemistry, Multidisciplinary
Eleftheria Poulou, Christian P. R. Hackenberger
Summary: This review highlights the groundbreaking discoveries and applications of Staudinger reactions in the molecular life sciences, including its engineering as a bioorthogonal reaction and its recent applications in generating next-generation biopharmaceuticals through modern bioconjugation methods.
ISRAEL JOURNAL OF CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Don S. Munasinghe, Marc-Andre Kasper, Radomir Jasinski, Karolina Kula, Marcin Palusiak, Malgorzata Celeda, Grzegorz Mloston, Christian P. R. Hackenberger
Summary: By utilizing the reactivity of ethynyl-phosphonites, novel P(V)-containing five-membered heterocycles were synthesized via (3+2)-cyclization reactions with aldehydes or cycloaliphatic thioketones, yielding satisfactory to excellent yields. The reactions with thioketones proceeded smoothly at room temperature without any catalyst, while the conversions with aldehydes required the addition of triethylamine as a base. A step-wise (3+2)-cyclization mechanism for the formation of the 1,3-thiaphosphole ring was proposed based on DFT quantum chemical calculations. This study introduces new cyclization reactions using unsaturated phosphonites as central synthetic building blocks to access stable phosphorus-containing heterocycles with unexplored potential in the molecular sciences.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Jan Vincent V. Arafiles, Jonathan Franke, Luise Franz, Jacobo Gomez-Gonzalez, Kristin Kemnitz-Hassanin, Christian P. R. Hackenberger
Summary: This study presents a powerful and efficient strategy for the intracellular delivery of functional cargoes. By increasing the retention on the cellular membrane, the authors found that CPP additives with a hydrophobic peptide sequence can enhance the uptake of protein cargoes without causing cytotoxicity. The results provide important design principles for cell-surface-retained CPP additives and demonstrate the potential of hydrophobic CPP additives in delivering fluorescent proteins and functional macrocyclic peptides.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Jacob Gorenflos L. Lopez, Peter Schmieder, Kristin Kemnitz-Hassanin, Hatice Ceyda Asikoglu, Arif Celik, Christian E. Stieger, Dorothea Fiedler, Stephan Hinderlich, Christian P. R. Hackenberger
Summary: This study introduces a real-time assay to monitor different enzymatic steps of sialic acid biosynthesis. The NMR techniques used in this study allow for the identification of characteristic signals and suggest that MNK phosphorylation reaction is exclusive for N-acetylmannosamine generated by GNE. Competition experiments reveal the preference of an N-acetylglucosamine-preferring kinase in the phosphorylation process.
Article
Chemistry, Multidisciplinary
Sarah Hansen, Jan Vincent V. Arafiles, Philipp Ochtrop, Christian P. R. Hackenberger
Summary: We report an efficient method to selectively install electrophilic ethynyl-phosphonamidates on peptides during solid phase peptide synthesis. The synthesized peptidic compounds, including a cell-penetrating peptide, showed high efficiency as an additive for cellular delivery of proteins.
CHEMICAL COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Anselm F. L. Schneider, Joerg Kallen, Johannes Ottl, Patrick C. Reid, Sebastien Ripoche, Stephan Ruetz, Therese-Marie Stachyra, Samuel Hintermann, Christoph E. Dumelin, Christian P. R. Hackenberger, Andreas L. Marzinzik
Summary: MDM2 is a crucial negative regulator of p53, and a macrocyclic ligand with picomolar potency on MDM2 was identified through a display technique. The unique binding mode and conjugation with a cyclic cell-penetrating peptide enhance the intracellular availability of cyclic peptides, demonstrating a potential approach for drug discovery projects utilizing intracellular tools.
RSC CHEMICAL BIOLOGY
(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)
