0000000000077575
AUTHOR
Kerstin Johann
showing 10 related works from this author
Enhanced Permeability and Retention-like Extravasation of Nanoparticles from the Vasculature into Tuberculosis Granulomas in Zebrafish and Mouse Mode…
2018
The enhanced permeability and retention (EPR) effect is the only described mechanism enabling nanoparticles (NPs) flowing in blood to reach tumors by a passive targeting mechanism. Here, using the transparent zebrafish model infected with Mycobacterium marinum we show that an EPR-like process also occurs allowing different types of NPs to extravasate from the vasculature to reach granulomas that assemble during tuberculosis (TB) infection. PEGylated liposomes and other NP types cross endothelial barriers near infection sites within minutes after injection and accumulate close to granulomas. Although similar to 100 and 190 nm NPs concentrated most in granulomas, even similar to 700 nm liposo…
Trans -Cyclooctene-Functionalized PeptoBrushes with Improved Reaction Kinetics of the Tetrazine Ligation for Pretargeted Nuclear Imaging
2020
Tumor targeting using agents with slow pharmacokinetics represents a major challenge in nuclear imaging and targeted radionuclide therapy as they most often result in low imaging contrast and high radiation dose to healthy tissue. To address this challenge, we developed a polymer-based targeting agent that can be used for pretargeted imaging and thus separates tumor accumulation from the imaging step in time. The developed targeting agent is based on polypeptide-graft-polypeptoid polymers (PeptoBrushes) functionalized with trans-cyclooctene (TCO). The complementary In-111-labeled imaging agent is a 1,2,4,5-tetrazine derivative, which can react with aforementioned TCO-modified PeptoBrushes i…
Radiolabeling of a polypeptide polymer for intratumoral delivery of alpha-particle emitter, 225Ac, and beta-particle emitter, 177Lu
2021
Introduction: Radiotherapy of cancer requires both alpha- and beta-particle emitting radionuclides, as these radionuclide types are efficient at destroying different types of tumors. Both classes of radionuclides require a vehicle, such as an antibody or a polymer, to be delivered and retained within the tumor. Polyglutamic acid (pGlu) is a polymer that has proven itself effective as a basis of drug-polymer conjugates in the clinic, while its derivatives have been used for pretargeted tumor imaging in a research setup. trans-Cyclooctene (TCO) modified pGlu is suitable for pretargeted imaging or therapy, as well as for intratumoral radionuclide therapy. In all cases, it becomes indirectly ra…
Tetrazine- and trans -cyclooctene-functionalised polypept(o)ides for fast bioorthogonal tetrazine ligation
2020
The inverse electron demand Diets-Alder (IEDDA) reaction-initiated ligation between 1,2,4,5-tetra-zines (Tz) and trans-cyclooctenes (TCO) is one of the fastest bioorthogonal reactions known today and is therefore increasingly used for in vivo click chemistry. Described herein is the synthesis of Tz- and TCO-functionalised polypeptides, polypeptoids and polypeptide-block-polypeptoids (polypept(o) ides) by ring-opening polymerisation of the corresponding N-carboxyanhydrides using Tz- or TCO-functional amine initiators. Despite the reactivity of tetrazines, polymers with low dispersity and high end group integrity can be obtained as observed by gel permeation chromatography (GPC), nuclear magn…
The zebrafish embryo as an in vivo model for screening nanoparticle-formulated lipophilic anti-tuberculosis compounds.
2021
ABSTRACT With the increasing emergence of drug-resistant Mycobacterium tuberculosis strains, new and effective antibiotics against tuberculosis (TB) are urgently needed. However, the high frequency of poorly water-soluble compounds among hits in high-throughput drug screening campaigns is a major obstacle in drug discovery. Moreover, in vivo testing using conventional animal TB models, such as mice, is time consuming and costly, and represents a major bottleneck in lead compound discovery and development. Here, we report the use of the zebrafish embryo TB model for evaluating the in vivo toxicity and efficacy of five poorly water-soluble nitronaphthofuran derivatives, which were recently id…
Investigation of α-amino acid N-carboxyanhydrides by X-ray diffraction for controlled ring-opening polymerization
2019
Abstract The need for a scalable synthesis of not sequence defined polypeptides as biomaterials is met by the ring-opening polymerization of α-amino acid N-carboxyanhydrides (NCAs). Even though this polymerization technique appears straight forward, it holds pitfalls in terms of reproducibility and overall control over the polymerization conditions, which depends, beside choice of solvent or initiator, significantly on reagent purity. In addition, the synthesis of monomers can lead to the formation of racemic amino acids. Thus, in this work, we describe the benefits of highly pure monomers in order to control nucleophilic ring-opening polymerization NCAs. Hereby, monomer purity is investiga…
CCDC 1874607: Experimental Crystal Structure Determination
2019
Related Article: Olga Schäfer, Dieter Schollmeyer, Alexander Birke, Regina Holm, Kerstin Johann, Christian Muhl, Christine Seidl, Benjamin Weber, Matthias Barz|2019|Tetrahedron Lett.|60|272|doi:10.1016/j.tetlet.2018.12.028
CCDC 1874606: Experimental Crystal Structure Determination
2019
Related Article: Olga Schäfer, Dieter Schollmeyer, Alexander Birke, Regina Holm, Kerstin Johann, Christian Muhl, Christine Seidl, Benjamin Weber, Matthias Barz|2019|Tetrahedron Lett.|60|272|doi:10.1016/j.tetlet.2018.12.028
CCDC 1874603: Experimental Crystal Structure Determination
2019
Related Article: Olga Schäfer, Dieter Schollmeyer, Alexander Birke, Regina Holm, Kerstin Johann, Christian Muhl, Christine Seidl, Benjamin Weber, Matthias Barz|2019|Tetrahedron Lett.|60|272|doi:10.1016/j.tetlet.2018.12.028
CCDC 1874604: Experimental Crystal Structure Determination
2019
Related Article: Olga Schäfer, Dieter Schollmeyer, Alexander Birke, Regina Holm, Kerstin Johann, Christian Muhl, Christine Seidl, Benjamin Weber, Matthias Barz|2019|Tetrahedron Lett.|60|272|doi:10.1016/j.tetlet.2018.12.028