DESIGN, SYNTHESIS, AND COMPLEXING PROPERTIES OF ((1)CYS-(1')CYS,(4)CYS-(4')CYS)-DITHIOBIS(AC-L-(1)CYS-L-PRO-D-VAL-L-(4)CYS-NH2) - THE 1ST EXAMPLE OF A NEW FAMILY OF ION-BINDING PEPTIDES

Controlled formation of two interchain disulfide bonds in peptides containing two cysteines affords dimers of well-defined topology. Such an approach has been used in the design and synthesis of the cyclic peptide (1Cys-1'Cys,4Cys-4'Cys)-dithiobis(Ac-L-1Cys-L-Pro-D-Val-L-4Cys-NH2) (1), inspired in the antibiotic valinomycin. The conformational and ion-binding properties of 1 have been investigated by nuclear magnetic resonance and circular dichroism spectroscopy. The cyclic peptide presents solvent- and temperature-dependent conformations and forms complexes in acetonitrile with barium cations with high affinity (log K(Ba2+) = 9.09 +/- 2.58) and considerable selectivity (log K(Sr2+) = 4.96 +/- 0.10; log K(Mg2+) = 4.07 +/- 0.07; log K(Ca2+) = 3.21 +/- 0.10 log K(Li+) = 2.60 +/- 0.04; log K(Na+) = 2.11 +/- 0.04). Computer-extracted circular dichroism spectra of the 1:1 complexes of 1 with alkali metal and alkali earth cations show that the conformation of the complexed peptide is determined by the size of the metal ion, indicating that there is good balance between flexibility and rigidity in the two strands held by the disulfide bridges.