Tetranuclear Cu(II)-chiral complexes: synthesis, characterization and biological activity

Tetranuclear chiral Cu(ii)-Schiff-base complexes S-1 and R-1, were synthesised using enantiomerically pure (S)-(H(2)vanPheol) and (R)-(H(2)vanPheol) ligands respectively in the ratio of 1 : 1 of Cu(NO(3))(2) to (S/R)-(H(2)vanPheol) in MeOH at room temperature. A pair of polynuclear chiral Cu(ii)-cluster complexes were characterized using single-crystal X-ray diffraction, elemental analysis, infrared and CD spectroscopy. The results revealed the importance of these chiral ligands encouraging the arrangement of copper metal in non-centrosymmetric polar packing. The potential of the novel [Cu(4)(S/R-vanPheol)(2)(S/R-HvanPheol)(2)(CH(3)OH)(2)](NO(3))(2) complexes as biologically active compounds was assessed in particular regarding their anti-proliferative and anti-microbial properties

O-Glycosylation of snails

The glycosylation abilities of snails deserve attention, because snail species serve as intermediate hosts in the developmental cycles of some human and cattle parasites. In analogy to many other host-pathogen relations, the glycosylation of snail proteins may likewise contribute to these host-parasite interactions. Here we present an overview on the O-glycan structures of 8 different snails (land and water snails, with or without shell): Arion lusitanicus, Achatina fulica, Biomphalaria glabrata, Cepaea hortensis, Clea helena, Helix pomatia, Limax maximus and Planorbarius corneus. The O-glycans were released from the purified snail proteins by β-elimination. Further analysis was carried out by liquid chromatography coupled to electrospray ionization mass spectrometry and – for the main structures – by gas chromatography/mass spectrometry. Snail O-glycans are built from the four monosaccharide constituents: N-acetylgalactosamine, galactose, mannose and fucose. An additional modification is a methylation of the hexoses. The common trisaccharide core structure was determined in Arion lusitanicus to be N-acetylgalactosamine linked to the protein elongated by two 4-O-methylated galactose residues. Further elongations by methylated and unmethylated galactose and mannose residues and/or fucose are present. The typical snail O-glycan structures are different to those so far described. Similar to snail N-glycan structures they display methylated hexose residues

Biogenesis and functions of bacterial S-layers.

The outer surface of many archaea and bacteria is coated with a proteinaceous surface layer (known as an S-layer), which is formed by the self-assembly of monomeric proteins into a regularly spaced, two-dimensional array. Bacteria possess dedicated pathways for the secretion and anchoring of the S-layer to the cell wall, and some Gram-positive species have large S-layer-associated gene families. S-layers have important roles in growth and survival, and their many functions include the maintenance of cell integrity, enzyme display and, in pathogens and commensals, interaction with the host and its immune system. In this Review, we discuss our current knowledge of S-layer and related proteins, including their structures, mechanisms of secretion and anchoring and their diverse functions

Towards Utilising Photocrosslinking of Polydiacetylenes for the Preparation of “Stealth” Upconverting Nanoparticles

We demonstrate a novel strategy for preparing hydrophilic upconverting nanoparticles (UCNPs) by harnessing the photocrosslinking ability of diacetylenes. Replacement of the hydrophobic oleate coating on the UCNPs with 10,12-pentacosadiynoic acid, followed by overcoating with diacetylene phospholipid and subsequent photocrosslinking under 254 nm irradiation produces water-dispersible polydiacetylene-coated UCNPs. These UCNPs resist the formation of a biomolecular corona and show great colloidal stability. Furthermore, amine groups on the diacetylene phospholipid allow for functionalisation of the UCNPs with, for example, radiolabels or targeting moieties. These results demonstrate that this new surface-coating method has great potential for use in the preparation of UCNPs with improved biocompatibility

Facile preparation of multifunctionalisable 'stealth' upconverting nanoparticles for biomedical applications

Pure hexagonal (β-phase) NaYF4-based hydrophobic upconverting nanoparticles (UCNPs) were surface-modified with O-phospho-l-threonine (OPLT), alendronic acid, and PEG-phosphate ligands to generate water-dispersible UCNPs. Fourier-transform infrared (FTIR) spectroscopy was used to establish the presence of the ligands on the UCNP surface. These UCNPs exhibit great colloidal stability and a near-neutral surface at physiological pH, as confirmed by dynamic light scattering (DLS) and zeta potential (ζ) measurements, respectively. The particles also display excellent long-term stability, with no major adverse effect on the size of UCNPs when kept at pH 7.4. Upon exposure to human serum, PEG-phosphate- and alendronate-coated UCNPs showed no formation of biomolecular corona, as confirmed by SDS-PAGE analysis. The photophysical properties of water-dispersible UCNPs were investigated using steady-state as well as time-resolved luminescence spectroscopy, under excitation at ca. 800 nm. The results clearly show that the UCNPs demonstrate bright upconversion (UC) luminescence. Furthermore, the presence of reactive groups on the NPs, such as free amine groups in alendronate-coated UCNPs, enables further functionalisation of UCNPs with, for example, small molecules, peptides, proteins, and antibodies. Overall these protein corona resistant UCNPs show great biocompatibility and are worthy of further investigation as potential new biomaging probes

Ultrasmall inorganic nanoparticles: State-of-the-art and perspectives for biomedical applications

Ultrasmall nanoparticulate materials with core sizes in the 1-3 nm range bridge the gap between single molecules and classical, larger-sized nanomaterials, not only in terms of spatial dimension, but also as regards physicochemical and pharmacokinetic properties. Due to these unique properties, ultrasmall nanoparticles appear to be promising materials for nanomedicinal applications. This review overviews the different synthetic methods of inorganic ultrasmall nanoparticles as well as their properties, characterization, surface modification and toxicity. We moreover summarize the current state of knowledge regarding pharmacokinetics, biodistribution and targeting of nanoscale materials. Aside from addressing the issue of biomolecular corona formation and elaborating on the interactions of ultrasmall nanoparticles with individual cells, we discuss the potential diagnostic, therapeutic and theranostic applications of ultrasmall nanoparticles in the emerging field of nanomedicine in the final part of this review

Design and Biological Evaluation of Small-Molecule PET-Tracers for Imaging of Programmed Death Ligand 1

Noninvasive molecular imaging of the PD-1/PD-L1 immune checkpoint is of high clinical relevance for patient stratification and therapy monitoring in cancer patients. Here we report nine small-molecule PD-L1 radiotracers with solubilizing sulfonic acids and a linker–chelator system, designed by molecular docking experiments and synthesized according to a new, convergent synthetic strategy. Binding affinities were determined both in cellular saturation and real-time binding assay (LigandTracer), revealing dissociation constants in the single digit nanomolar range. Incubation in human serum and liver microsomes proved in vitro stability of these compounds. Small animal PET/CT imaging, in mice bearing PD-L1 overexpressing and PD-L1 negative tumors, showed moderate to low uptake. All compounds were cleared primarily through the hepatobiliary excretion route and showed a long circulation time. The latter was attributed to strong blood albumin binding effects, discovered during our binding experiments. Taken together, these compounds are a promising starting point for further development of a new class of PD-L1 targeting radiotracers