8,228 research outputs found
Asymmetric triplex metallohelices with high and selective activity against cancer cells
Small cationic amphiphilic α-helical peptides are emerging as agents for the treatment of cancer and infection, but they are costly and display unfavourable pharmacokinetics. Helical coordination complexes may offer a three-dimensional scaffold for the synthesis of mimetic architectures. However, the high symmetry and modest functionality of current systems offer little scope to tailor the structure to interact with specific biomolecular targets, or to create libraries for phenotypic screens. Here, we report the highly stereoselective asymmetric self-assembly of very stable, functionalized metallohelices. Their anti-parallel head-to-head-to-tail ‘triplex’ strand arrangement creates an amphipathic functional topology akin to that of the active sub-units of, for example, host-defence peptides and p53. The metallohelices display high, structure-dependent toxicity to the human colon carcinoma cell-line HCT116 p53++, causing dramatic changes in the cell cycle without DNA damage. They have lower toxicity to human breast adenocarcinoma cells (MDA-MB-468) and, most remarkably, they show no significant toxicity to the bacteria methicillin-resistant Staphylococcus aureus and Escherichia coli.
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Multi-Omic Profiling of Melophlus Sponges Reveals Diverse Metabolomic and Microbiome Architectures that Are Non-overlapping with Ecological Neighbors.
Marine sponge holobionts, defined as filter-feeding sponge hosts together with their associated microbiomes, are prolific sources of natural products. The inventory of natural products that have been isolated from marine sponges is extensive. Here, using untargeted mass spectrometry, we demonstrate that sponges harbor a far greater diversity of low-abundance natural products that have evaded discovery. While these low-abundance natural products may not be feasible to isolate, insights into their chemical structures can be gleaned by careful curation of mass fragmentation spectra. Sponges are also some of the most complex, multi-organismal holobiont communities in the oceans. We overlay sponge metabolomes with their microbiome structures and detailed metagenomic characterization to discover candidate gene clusters that encode production of sponge-derived natural products. The multi-omic profiling strategy for sponges that we describe here enables quantitative comparison of sponge metabolomes and microbiomes to address, among other questions, the ecological relevance of sponge natural products and for the phylochemical assignment of previously undescribed sponge identities
Acceleration of stereo-matching on multi-core CPU and GPU
This paper presents an accelerated version of a
dense stereo-correspondence algorithm for two different parallelism
enabled architectures, multi-core CPU and GPU. The
algorithm is part of the vision system developed for a binocular
robot-head in the context of the CloPeMa 1 research project.
This research project focuses on the conception of a new clothes
folding robot with real-time and high resolution requirements
for the vision system. The performance analysis shows that
the parallelised stereo-matching algorithm has been significantly
accelerated, maintaining 12x and 176x speed-up respectively
for multi-core CPU and GPU, compared with non-SIMD singlethread
CPU. To analyse the origin of the speed-up and gain
deeper understanding about the choice of the optimal hardware,
the algorithm was broken into key sub-tasks and the performance
was tested for four different hardware architectures
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