Metallohelices: design, self-assembly, biomedicine
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Metallohelices: potential mimetics of α-helical peptides in cancer treatment?, Future Medicinal Chemistry, Future Science

Metallohelices: potential mimetics of α-helical peptides in cancer treatment?, Future Medicinal Chemistry, Future Science | Metallohelices: design, self-assembly, biomedicine | Scoop.it
Scott Group's insight:

It is nearly 30 years since Lehn et al. posited the
idea that helicates bore a resemblance to natural
α-helices, but it is only recently that they have
been approaching the point at which they may be
considered to be α-helix
mimetic.

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Genetic Eng & Biotech News: Stable Metallohelices Self-Assemble, Fight Cancer

Genetic Eng & Biotech News: Stable Metallohelices Self-Assemble, Fight Cancer | Metallohelices: design, self-assembly, biomedicine | Scoop.it
Artificial anticancer molecules mimic the properties of one of the body's natural defense systems.
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Helicates: Making head-head-tails of it : Nature Chemistry

Helicates: Making head-head-tails of it : Nature Chemistry | Metallohelices: design, self-assembly, biomedicine | Scoop.it

"These findings offer a potential route for overcoming some of the problems faced during the development of cancer therapies"

Scott Group's insight:

Markus Albrecht on our anticancer triplex metallohelices work

 

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JACS: Chiral metallo-helical complexes enantioselectively target amyloid β for treating Alzheimer’s disease

JACS: Chiral metallo-helical complexes enantioselectively target amyloid β for treating Alzheimer’s disease | Metallohelices: design, self-assembly, biomedicine | Scoop.it

"... this is the first report of enantioselective inhibition of Aβ aggregation.... the chiral metal complex can cross the blood-brain barrier ...opens a new avenue for design and screening of chiral agents as Aβ inhibitors against AD."

Scott Group's insight:

Our collaborator Xiaogang Chu and co-workers show that two flexicates selectively bind to a protein amyloid-β which is implicated in the mechanism of Alzheimer's disease

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Nature Chem: Optically pure, water-stable metallo-helical ‘flexicate’ assemblies with antibiotic activity

Nature Chem: Optically pure, water-stable metallo-helical ‘flexicate’ assemblies with antibiotic activity | Metallohelices: design, self-assembly, biomedicine | Scoop.it

"... a highly versatile approach for preparing a range of metal–ligand assemblies that are helical, optically pure and stable in aqueous solutions. One such iron(II) ‘flexicate’ system exhibits significant interactions with DNA, as well as promising antimicrobial activity properties."

Scott Group's insight:

In 2011 we developed a way of making helicate-like molecules, based on Fe(II) and simple organic components, that could give a much wider range of complexes than had been achieved before. They also had the very important properties of being optically pure and compatible with water. 

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Dalton: Optically pure heterobimetallic helicates from self-assembly and click strategies

Dalton: Optically pure heterobimetallic helicates from self-assembly and click strategies | Metallohelices: design, self-assembly, biomedicine | Scoop.it

"... homohelical (ΔFe,ΔCu) configured systems with unusual trigonal planar Cu cations are formed exclusively .... clean CuAAC reactions [give] the first optically pure heterohelicates."

Scott Group's insight:

Helicates, and our flexicate systems, have quite high symmetry. We have been looking for ways of making optically pure helicates of lower symmetry. This work was featured as a Front Cover with graphic design by Elisabeth Heissler.

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Left-handed Corkscrew Structure Helps Combat MRSA, May Someday Open Bottles

Left-handed Corkscrew Structure Helps Combat MRSA, May Someday Open Bottles | Metallohelices: design, self-assembly, biomedicine | Scoop.it
Researchers at the University of Warwick, in the UK, have succeeded in adopting the helical structure of a corkscrew to create a new synthetic class of mol
Scott Group's insight:

We were not really trying to adopt the corkscrew architecture here. It's just that metal complexes are often inherently chiral, so if you are trying to make systems for medicinal applications then it is important to control the chirality. The fact that the lleft-handed helix was a better antibiotic is something we don't understand yet. 

 

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Chirality could be key to overcoming antibiotic resistance

Chirality could be key to overcoming antibiotic resistance | Metallohelices: design, self-assembly, biomedicine | Scoop.it
‘Flexicates’ are active against MRSA and E.coli, but have low toxicity
Scott Group's insight:

One of a large number of trade and similar magazines that picked up our flexicate work

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Nature Chemistry: Asymmetric triplex metallohelices with high and selective activity against cancer cells

Nature Chemistry: Asymmetric triplex metallohelices with high and selective activity against cancer cells | Metallohelices: design, self-assembly, biomedicine | Scoop.it
Water-soluble metallohelices containing an antiparallel head-to-head-to-tail arrangement of strands are reported. This amphipathic functional topology is akin to that of host-defence peptides. The metallohelices show high and selective toxicity to a cancer cell line, causing dramatic changes in the cell cycle without DNA damage. In contrast, there is no significant toxicity to MRSA and Escherichia coli.
Scott Group's insight:

We describe a method by which amphipathic metallohelices with peptidomimetic structures can be designed and prepared. A large range of compounds produced includes some highly selective anticancer candidates.

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Nature: Science-Business eXchange

Nature: Science-Business eXchange | Metallohelices: design, self-assembly, biomedicine | Scoop.it
Asymmetric triplex metallohelices could be useful for treating cancer.
Scott Group's insight:

Asymmetric triplex metallohelices nhibited proliferation in a human colon carcinoma cell line with an IC50 value of 500 nM without inducing DNA damage. Next steps include synthesizing additional metallohelices and elucidating their mechanism of action.

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Meet the 'Lego Death Star' Designed to Kill Cancer Dead

Meet the 'Lego Death Star' Designed to Kill Cancer Dead | Metallohelices: design, self-assembly, biomedicine | Scoop.it
Self-assembling molecules promise to fortify the body's natural anti-cancer defenses.
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Chem Sci: Metallohelices with activity against cisplatin-resistant cancer cells; does the mechanism involve DNA binding?

Chem Sci: Metallohelices with activity against cisplatin-resistant cancer cells; does the mechanism involve DNA binding? | Metallohelices: design, self-assembly, biomedicine | Scoop.it

"Enantiomers of a relatively rigid DNA-binding metallo-helix are shown to have comparable activity to that of cisplatin against the cell lines MCF7 (human breast adenocarcinoma) and A2780 (human ovarian carcinoma) but are ca five times more active against the cisplatin-resistant A2780cis."

Scott Group's insight:

Previous helicates have been shown to bind to naked DNA, but it is not known that this has anything to do with their biological activity. In this paper - our first on cancer, in collaboration with Roger Phillips, Patrick C McGowan and Viktor Brabec - we demonstrate many types of DNA binding with flexicates but find some compounds where DNA binding cannot be involved. 

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Nature Chem: Resolutely pure helices

Nature Chem: Resolutely pure helices | Metallohelices: design, self-assembly, biomedicine | Scoop.it
Helical coordination compounds that show promising antibiotic activity in aqueous media have been assembled directly in their optically pure form, without the need for a resolution step.
Scott Group's insight:

Janice Aldrich-Wright's views on our flexicate work...

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Future Medicine: Flexicate molecules as a potential new class of antibiotics

Future Medicine: Flexicate molecules as a potential new class of antibiotics | Metallohelices: design, self-assembly, biomedicine | Scoop.it
Scott Group's insight:

This is an evaluation of our work by NIH scientists Frank R DeLeo and co-workers...

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Left-handed iron corkscrews point the way to new weapon in battle against superbugs like MRSA

Left-handed iron corkscrews point the way to new weapon in battle against superbugs like MRSA | Metallohelices: design, self-assembly, biomedicine | Scoop.it
Scientists at The University to develop a new weapon in the fight against infections like E-coli and MRSA.
Scott Group's insight:

This is Warwick's press release. Suzanne on the left did most of the chemistry and biophysics for this paper. She eventually won the Warwick Chemistry Thesis Prize for this work.  

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