title: Alkaline earth metal ion induced coil-helix-coil transition of lysine-coumarin-azacrown hybrid foldamers with OFF-OFF-ON fluorescence switching.
abstract: A new metal-ion-responsive and fluorescent foldamer, OPLM(8), composed of eight lysine-coumarin-azacrown units, has been designed and synthesized. The flexible OPLM(8) can be forced into a well-defined helix structure only upon the addition of alkaline earth metal ions. The structural change is based on the crown ether moieties being positioned in the requisite arrangement along the peptide chain, that is, at i, i+4 spacing, such that the alkaline earth metal ions can mediate the formation of four sandwich complexes between them. Moreover, varying the chelator-to-metal-ion ratio from 2:1 to 1:1 resulted in disassembly of the sandwich complexes leading to collapse of the helical structure to a random coil. These metal-ion-induced structural transitions could not only be monitored by the CD amplitude change but also easily probed by unique "OFF-OFF-ON" fluorescence intensity changes from 0.7-fold to 14-fold as the structure changed from the folded helix to a random coil. To further verify that the helix formation was indeed induced by metal-ion complexation, two kinds of control octamers with only four metal-ion chelators on the side chains were studied. One, which was capable of forming two sandwich complexes between the i and i+4 residues, displayed a negative Cotton couplet with the magnitude of its A value close to half that of OPLM(8), and the second had four metal-ion chelators positioned in the same turn, and hence was incapable of forming intramolecular metal complexes and showed different induced CD signals. Collectively, the photospectroscopic data and the results of the control studies suggest that alkaline earth metal ions can efficiently promote the flexible octamer OPLM(8) into a well-organized helix by the formation of sandwich complexes between substituents at an i, i+4 spacing.
authors.affiliation: Department of Chemistry, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei, 10617 Taiwan, ROC.
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Lin
authors.forename: Chao-Tsen
authors.initials: CT
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D003374:Coumarins / Q000737:chemistry*; D005453:Fluorescence; D007477:Ions / Q000737:chemistry*; D008239:Lysine / Q000737:chemistry*; D008670:Metals / Q000737:chemistry*; D008673:Metals, Alkaline Earth / Q000737:chemistry*; D015394:Molecular Structure
chemical_list: D003374:Coumarins; D007477:Ions; D008670:Metals; D008673:Metals, Alkaline Earth; C030123:coumarin; D008239:Lysine