The Solution Structure of a Copper(II) Compound of a New Cyclic Octapeptide by EPR Spectroscopy and Force Field Calculations

Abstract

A new cyclic octapeptide, cyclo(Ile-Ser-(Gly)Thz-Ile-Thr-(Gly)Thz) (PatN), related to patellamide A, has been synthesized and reacted with copper(II) and base to form mono- and dinuclear complexes. The coordination environments around copper(II) have been characterized by EPR spectroscopy. The solution structure of the thermodynamically most stable product, a purple dicopper(II) compound, has been examined by simulating weakly dipole-dipole coupled EPR spectra based upon structural parameters obtained from force field (MM and MD) calculations. The MM-EPR method produces a saddle-shaped structure for [Cu(2)(PatN)(OH(2))(6)] that is similar to the known solution structure of patellamide A and the known solid-state structure of [Cu(2)(AscidH(2))CO(3)(OH(2))(2)]. Compared with the latter, [Cu(2)(PatN)] has no carbonate bridge and a significantly flatter topology. The MM-EPR approach to solution-structure determination for paramagnetic metallopeptides may find wide applications to other metallopeptides and metalloproteins.

Cyclic peptide marine metabolites and CuII

“…The observation that, despite the biotoxicity of Cu II , its concentration in the ascidians is roughly 10 4 times higher than in the surrounding sea water, has fostered the interest in the macromolecule's metal ion, and especially Cu II coordination chemistry. 34,[43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59] The focus of this perspective is on the Cu II coordination chemistry of the L. patella and L. bistratum cyclic peptides and a series of synthetic analogues. Structure and dynamics of the metal-free ligands and their applications are also reviewed.…”

“…124 The binding constants for a series of cyclic peptides from L. patella and L. bistratum together with synthetic analogues are assembled in Table 1 , Scheme 2; the heterocycles of these ligands were not closed so far although this should be feasible). 48,53 These syntheses were quite tedious and did not yield sufficient quantities of the ligands for comprehensive studies of the solution coordination chemistry. However, based on ESI-MS, electronic (UV-vis-NIR and CD) and EPR spectroscopy, we have been able to fully characterize the main mono-and dinuclear species in solution.…”

Copper(II) Coordination Chemistry of Westiellamide and Its Imidazole, Oxazole, and Thiazole Analogues

“…Therefore, a small value of A k is expected. [8,[44][45][46][47] IR spectroscopy: Upon coordination of H 3 L 1 to copper(II), there is a shift of the CO peptide vibrational band in the IR spectrum from 1656 cm À1 in the metal-free macrocycle to 1617 cm À1 in the copper(II) complex. Such a shift would be expected for the substitution of hydrogen of a peptide group by a metal ion.…”

Density functional theory studies of oxygen and carbonate binding to a dicopper patellamide complex

“…The basic structure of patellamides consists of a cyclic octapeptide containing two thiazole and two oxazoline rings (Scheme 1). The structure binds two metal atoms, typically copper atoms although studies of other bound metals have been reported as well [36][37][38][39][40]. The patellamides are split into two classes, symmetric and asymmetric, distinguished from each other by the absence or presence of a phenylalanine residue, respectively.…”