| Autor: |
Faulkner AD; 1] Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK [2]., Kaner RA; 1] Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK [2]., Abdallah QM; College of Pharmacy, Taif University, PO Box 888, 21974 Taif, Saudi Arabia., Clarkson G; Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK., Fox DJ; Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK., Gurnani P; Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK., Howson SE; Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK., Phillips RM; Institute of Cancer Therapeutics, University of Bradford, Bradford BD7 1DP, UK., Roper DI; School of Life Sciences, Gibbet Hill Campus, University of Warwick, Coventry CV4 7AL, UK., Simpson DH; 1] Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK [2] School of Life Sciences, Gibbet Hill Campus, University of Warwick, Coventry CV4 7AL, UK., Scott P; Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK. |
| Abstrakt: |
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. |
