0000000001307297
AUTHOR
Tobias Bauer
Secondary Structure-Driven Hydrogelation Using Foldable Telechelic Polymer-Peptide Conjugates.
The synthesis of ABA and ABA' triblock polyethylene glycol-and polysarcosine-peptide conjugates is reported. The A/A' peptides are based on phenylalanine(F)-histidine(H) pentapeptide sequences FHFHF, which promote pH-switchable β-sheet self-assembly into nanorods in water. Only parallel β-sheet-driven folding and intermolecular assembly using ABA triblock polymer-peptide conjugates leads to interstrand cross-linking and hydrogelation, highlighting the impact of supramolecular interactions-directed structure formation at the nano- and mesoscopic level.
Kinetically Controlled Stepwise Self-Assembly of AuI-Metallopeptides in Water
The combination of attractive supramolecular interactions of a hydrophobic AuI-metallopeptide with the shielding effect of flexible oligoethylene glycol chains provides access to a stepwise self-assembly of a AuI-metalloamphiphile in water. Kinetic control of the supramolecular polymer morphology is achieved using a temperature-dependent assembly protocol, which yields low dispersity supramolecular polymers (metastable state I) or helical bundled nanorods (state II).
Zebrafish Embryos Allow Prediction of Nanoparticle Circulation Times in Mice and Facilitate Quantification of Nanoparticle–Cell Interactions
The zebrafish embryo is a vertebrate well suited for visualizing nanoparticles at high resolution in live animals. Its optical transparency and genetic versatility allow noninvasive, real-time observations of vascular flow of nanoparticles and their interactions with cells throughout the body. As a consequence, this system enables the acquisition of quantitative data that are difficult to obtain in rodents. Until now, a few studies using the zebrafish model have only described semiquantitative results on key nanoparticle parameters. Here, a MACRO dedicated to automated quantitative methods is described for analyzing important parameters of nanoparticle behavior, such as circulation time and…
Functionalization of P3HT with Various Mono- and Multidentate Anchor Groups
Due to its favorable optoelectronic properties and the accessibility via Grignard metathesis (GRIM) polymerization, poly(3-hexylthiophene) (P3HT) is one of the most applied conjugated polymers. The ‘living' nature of GRIM polymerization enables the modification of the polymer and the installation of desired properties. In the present study, two versatile approaches for the synthesis of anchor group-modified P3HT have been developed, which enable the functionalization of various inorganic nanoparticles. Depending on the polymerization conditions, mono- and bifunctional ethynyl-terminated P3HT or solely monofunctionalized aldehyde-terminated P3HT was synthesized. Afterwards, the quantitative …
Impact of Branching on the Solution Behavior and Serum Stability of Starlike Block Copolymers.
The size control of nanomedicines for tumor diagnosis and therapy is of high importance, since it enables or disables deep and sufficient tumor penetration. Amphiphilic star-shaped block copolypept(o)ides offer substantial promise to precisely adjust the hydrophobic core and the hydrophilic corona, independent of each other, and therefore simultaneously control the size dimension in the interesting size range from 10 to 30 nm. To gain access to core-shell structures of such sizes, 3-arm and 6-arm PeptoStars, based on poly(gamma-tert-butyloxycarbonyl-L-glutamate)-b-polysarcosine (pGlu(OtBu)-b-pSar), were prepared via controlled living ring-opening polymerization (ROP) of the corresponding N-…
Coordinative Binding of Polymers to Metal-Organic Framework Nanoparticles for Control of Interactions at the Biointerface
Metal-organic framework nanoparticles (MOF NPs) are of growing interest in diagnostic and therapeutic applications, and due to their hybrid nature, they display enhanced properties compared to more established nanomaterials. The effective application of MOF NPs, however, is often hampered by limited control of their surface chemistry and understanding of their interactions at the biointerface. Using a surface coating approach, we found that coordinative polymer binding to Zr- fum NPs is a convenient way for peripheral surface functionalization. Different polymers with biomedical relevance were assessed for the ability to bind to the MOF surface. Carboxylic acid and amine containing polymers…
Tetrazine- and trans -cyclooctene-functionalised polypept(o)ides for fast bioorthogonal tetrazine ligation
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…
Sekundärstrukturbildung als Triebkraft für die Selbstorganisation reaktiver Polypept(o)ide: Steuerung von Größe, Form und Funktion kernvernetzter Nanostrukturen
Prazise Kontrolle uber Morphologie und Funktion polymerer Nanostrukturen im Rahmen der Selbstorganisation stellt nach wie vor eine Herausforderung im Feld der Material- und biomedizinischen Wissenschaften dar, insbesondere wenn unabhangige Kontrolle uber einzelne Partikeleigenschaften erwunscht ist. Hier wird uber Sekundarstruktur-gesteuerte Selbstorganisation von Nanostrukturen basierend auf amphiphilen Blockcopolypept(o)iden berichtet und eine Strategie zur bio-reversiblen Einstellung der Kernpolaritat und –funktion unabhangig von der Partikelpraparation vorgestellt. Der Peptiden eigene Prozess der Sekundarstrukturbildung erlaubt so die Herstellung spharischer und wurmartiger kernvernetzt…
Poly(S-ethylsulfonyl-l-homocysteine): An α-Helical Polypeptide for Chemoselective Disulfide Formation
Homocysteine and cysteine are the only natural occurring amino acids that are capable of disulfide bond formations in peptides and proteins. The chemoselective formation of asymmetric disulfide bonds, however, is chemically challenging and requires an activating group combining stability against hard nucleophiles, e.g., amines, with reactivity toward thiols and soft nucleophiles. In light of these considerations, we introduced the S-alkylsulfonyl cysteines in our previous work. Here, we present the synthesis and ring-opening polymerization of S-ethylsulfonyl-l-homocysteine N-carboxyanhydrides. We demonstrate that the polymerization leads to narrowly distributed polypeptides (Đ = 1.1–1.3) wi…
Old proteins - new locations: myoglobin, haemoglobin, neuroglobin and cytoglobin in solid tumours and cancer cells
Aim: The unexpected identification of myoglobin (MB) in breast cancer prompted us to evaluate the clinico-pathological value of MB, haemoglobin (HB) and cytoglobin (CYGB) in human breast carcinoma cases. We further screened for the presence of neuroglobin (NGB) and CYGB in tumours of diverse origin, and assessed the O2-response of HB, MB and CYGB mRNAs in cancer cell lines, to better elicit the links between this ectopic globin expression and tumour hypoxia. Methods: Breast tumours were analysed by immunohistochemistry for HB, MB and CYGB and correlated with clinico-pathological parameters. Screening for CYGB and NGB mRNA expression in tumour entities was performed by hybridization, quant…
Core-shell functionalized zirconium-pemetrexed coordination nanoparticles as carriers with a high drug content
Selected drug molecules with Lewis base functions can be assembled into coordinative nanoparticles (NPs) by linking them with suitable metal ions. Such nanomaterials exhibit a high material economy due to high drug contents and minor amounts of inactive additives. The antifolate pemetrexed (PMX) which is used for the treatment of lung cancers contains two carboxy functions that are able to undergo coordinative binding of metal ions. This study presents the development of a multilayer PMX NP system where each layer serves a distinct purpose. The metal-drug NP core is assembled in a bottom-up approach by coordinative interactions between zirconium (IV) ions and PMX molecules. Since the NP cor…
Secondary-Structure-Driven Self-Assembly of Reactive Polypept(o)ides: Controlling Size, Shape, and Function of Core Cross-Linked Nanostructures.
Achieving precise control over the morphology and function of polymeric nanostructures during self-assembly remains a challenge in materials as well as biomedical science, especially when independent control over particle properties is desired. Herein, we report on nanostructures derived from amphiphilic block copolypept(o)ides by secondary-structure-directed self-assembly, presenting a strategy to adjust core polarity and function separately from particle preparation in a bioreversible manner. The peptide-inherent process of secondary-structure formation allows for the synthesis of spherical and worm-like core-cross-linked architectures from the same block copolymer, introducing a simple y…
CCDC 1858028: Experimental Crystal Structure Determination
Related Article: Christian Muhl, Olga Schäfer, Tobias Bauer, Hans-Joachim Räder, Matthias Barz|2018|Macromolecules|51|8188|doi:10.1021/acs.macromol.8b01442
CCDC 1858027: Experimental Crystal Structure Determination
Related Article: Christian Muhl, Olga Schäfer, Tobias Bauer, Hans-Joachim Räder, Matthias Barz|2018|Macromolecules|51|8188|doi:10.1021/acs.macromol.8b01442
CCDC 2002425: Experimental Crystal Structure Determination
Related Article: Tobias Bauer, Christian Muhl, Dieter Schollmeyer, Matthias Barz|2020|Macromol.Rapid Commun.||2000470|doi:10.1002/marc.202000470