A versatile, bottom-up approach allows the controlled fabrication of polydopamine (PD) nanostructures on DNA origami. PD is a biosynthetic polymer that has been investigated as an adhesive and promising surface coating material. However, the control of dopamine polymerization is challenged by the multistage-mediated reaction mechanism and diverse chemical structures in PD.DNA origami decorated with multiple horseradish peroxidase-mimicking DNAzyme motifs was used to control the shape and size of PD formation with nanometer resolution. These fabricated PD nanostructures can serve as “supramolecular glue” for controlling DNA origami conformations. Facile liberation of the PD nanostructures from the DNA origami templates has been achieved in acidic medium. This presented DNA origami controlled polymerization of a highly cross-linked polymer provides a unique access towards anisotropic PD architectures with distinct shapes that were retained even in the absence of the DNA origami template.
The authors are grateful to the financial support by the European Research Council (ERC) under the program Synergy Grant 319130-BioQ and the BMBF project “Selekomm” within the Biotechnologie 2020 + initiative.
We report site specific dual functionalizations of peptides and proteins capitalizing on reactivity differences of cysteines in their free (thiol) and protected, oxidized (disulfide) forms. The dual functionalization of interleukin 2 and EYFP proceeded with no loss of bioactivity in a stepwise fashion applying maleimide and disulfide rebridging allyl-sulfone groups. In order to ensure broader applicability of the functionalization strategy, a novel, short peptide sequence that introduces a disulfide bridge was designed and site-selective dual labeling in the presence of biogenic groups was successfully demonstrated.
The article is a collaboration with researchers at the Institute of Inorganic Chemistry I and Institute of Biophysics/Ulm University (Germany), the Key Laboratory of Advanced Technologies of Materials/School of Materials Science and Engineering/Southwest Jiaotong University (China) and the Department of Dermatology/University Medical Center Mainz/Johannes Gutenberg-University Mainz (Germany).
The authors are grateful to the financial support by the German Research Foundation (DFG), the ERC Synergy Grant 319130-BioQ, the Horizon2020 project“Hyperdiamond”, the Horizon2020 Marie Curie ITN ProteinConjugates and LGFG scholarship from Ulm University.
Self-assembly in situ, where synthetic molecules are programmed to organize in a complex environment can be a unique strategy to influence cellular functions. Here we present oligothiophene analogues that target, locate and dynamically self-report their supramolecular behavior within the confinement of a cell. Through the recognition of their chemical structure, we show that the cell provides different pathways for self-assembly that are traced with fluorescence microscopy. Their molecular organization emits in distinct fluorescent bands and the control each form is achieved by time, temperature as well as the use of the intracellular transport inhibitor, bafilomycin A1. We show the importance of both intrinsic and extrinsic factors for self-organization and the potential of such a platform toward developing synthetic functional components within living cells.
The article is a collaboration with researchers at the Institute of Organic Chemistry III/Ulm University, Institute of Molecular Biology Mainz, and Institute of Pharmacology and Toxicology/Ulm University Medical Center.
The authors are grateful to the financial support by the ERC Synergy grant 319130-BioQ and the Horizon2020 project Hyperdiamond.
In osteoporosis, bone structure can be improved by the introduction of therapeutic molecules inhibiting bone resorption by osteoclasts. Here, biocompatible hydrogels represent an excellent option for the delivery of pharmacologically active molecules to the bone tissue because of their biodegradability, injectability, and manifold functionalization capacity. The present study reports the preparation of a multifunctional hybrid hydrogel from chemically modified human serum albumin and rationally designed DNA building blocks. The hybrid hydrogel combines advantageous characteristics, including rapid gelation through DNA hybridization under physiological conditions and a self-healing and injectable nature with the possibility of specific loading and spatiotemporally controlled release of active proteins, making it an advanced biomaterial for the local treatment of bone diseases, for example, osteoporosis.
The article is a collaboration with researchers at the Institute of Organic Chemistry III/Ulm University, Institute of Orthopedic Research and Biomechanics/Trauma Research Center/Ulm University, Institute of Pharmacology and Toxicology/Ulm University, Key Laboratory of Organic Optoelectronics and Molecular Engineering of the Ministry of Education/Department of Chemistry/Tsinghua University (Beijing, China), and School of Chemistry and Chemical Engineering/Huazhong University of Science and Technology (Wuhan, China).
The authors are grateful to the financial support by the Horizon 2020 project “AD GUT” and by the German Research Foundation (DFG) in the framework of the Collaborative Research Center CRC1149 as well as the National Natural Science Foundation of China.
We report a bioinspired multifunctional albumin derived polypeptide coating comprising grafted poly(ethylene oxide) chains, multiple copies of the HIV TAT derived peptide enabling cellular uptake as well as mitochondria targeting triphenyl-phosphonium (TPP) groups. Exploring these polypeptide copolymers for passivating gold nanoparticles (Au NPs) yielded (i) NIR-emitting markers in confocal microscopy and (ii) photo-thermal active probes in optical coherence microscopy. We demonstrate the great potential of such multifunctional protein-derived biopolymer coatings for efficiently directing Au NP into cells and to subcellular targets to ultimately probe important cellular processes such as mitochondria dynamics and vitality inside living cells.
Organelle-targeted photosensitization represents a promising approach in photodynamic therapy where the design of the active photosensitizer (PS) is very crucial. In this work, we developed a macromolecular PS with multiple copies of mitochondria-targeting groups and ruthenium complexes that displays highest phototoxicity toward several cancerous cell lines. In particular, enhanced anticancer activity was demonstrated in acute myeloid leukemia cell lines, where significant impairment of proliferation and clonogenicity occurs. Finally, attractive two-photon absorbing properties further underlined the great significance of this PS for mitochondria targeted PDT applications in deep tissue cancer therapy.