Marine metabolites and metal ion chelation. Circular dichroism studies of metal binding to Lissoclinum cyclopeptides

Abstract

Variable temperature circular dichroism (CD) spectra of the patellamides A (3), B (4) and E (5), isolated from the ascidian ('sea squirt') Lissoclinum patella, show that they have very similar thermodynamically preferred macrocyclic ring conformations. In addition, the CD profile of the 'figure eight like' conformation 10 in the patellamides has been defined, and CD spectroscopy is shown to provide an insight into the interconversions between the limiting conformations, 9 and 10, in this family of cyclopeptides. The cyclopeptides 3-5 bind both Cu 2؉ and Zn 2؉ and CD studies show that as a family, in line with previous studies, they can bind more than one metal ion per molecule. Thus, the first binding domain for the three patellamides shows a binding constant in the range 2 × 10 4 to 2 × 10 5 , and a second binding site for patellamide B (4) has K ‫؍‬ 230 (Cu 2؉ ) and K ‫؍‬ 16-20 (Zn 2؉ ). The CD spectra of the patellamide-metal conjugates can be correlated with the 'square form' conformation 9 of the cyclopeptides. This best fit situation vis-à-vis metal chelation, could have important implications regarding the biological activity and modus operandi of the cyclopeptides in vivo.

Regulation of Hsp90 ATPase Activity by the Co-chaperone Cdc37p/p50

“…For a single binding site at equilibrium, the CD, expressed in ⌬A, at any wavelength is proportional to the concentration of the bound and unbound species of the host (H) and ligand (L) components (as shown in Equation 1) (24).…”

“…The spectropolarimeter was calibrated with ammonium d-champor-10-sulfonate. The dissociation constant K d was determined by analyzing the CD data using a non-linear regression analysis as described previously (6,24).…”

Formation of mononuclear and chloro-bridged binuclear copper(II) complexes of patellamide D, a naturally occurring cyclic peptide: influence of anion and solvent

“…The recognition of the potential role of cyclic peptides of marine origin as ionophores in biological systems has prompted a number of studies of the complexation reactions of these peptides with the transition and non-transition elements [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]. Studies of the metal binding properties of these molecules have been suggested to have important implications regarding the biological activity of these compounds in vivo, [13,17] and one study has suggested that copper(II) is the biologically relevant metal for the patellamides, one class of these peptides [14].…”

Cyclic peptide marine metabolites and CuII

“…Initial reasons for investigation included the coordination chemistry of the individual metal ions, understanding the electronic structures, stabilities and selectivity with particular metal ions, and recent efforts have been directed increasingly towards reactivities to elucidate the possible biological functions of these peptides and complexes. 34,[43][44][45][46][47]49,61,67,94,[110][111][112][113] There is a distinct difference between various species with respect to the heterocycles involved in the cyclic peptides, and this must lead to differences in the corresponding transition metal coordination chemistry, specifically also in terms of electronic structures, stabilities and reactivities and therefore might have some influence in the biological activity. The L. bistratum derived macrocycles include oxazoline-based cyclic pseudo-hexapeptides (e.g.…”