A Novel Potassium-Binding Hydrolysis Product of Ascidiacyclamide:  A Cyclic Octapeptide Isolated from the Ascidian Lissoclinum patella

Abstract

A new octapeptide has been isolated and characterized as its potassium complex from acidic aqueous methanol solutions of ascidiacyclamide, a cyclic peptide isolated from the ascidian Lissoclinum patella. Crystals suitable for X-ray structure determination were orthorhombic, space group P2(1)2(1)2(1), with a = 15.442(3) Å, b = 36.167(1) Å, c = 9.567(3) Å, V = 5343(2) Å(3), Z = 4, and R = 0.069. The structure consists of the macrocyclic cation, three perchlorate anions, and two water molecules. The macrocyclic ring of ascidiacyclamide remains intact, but two oxazoline rings have been opened to form two amino lactones, with the amine protonated. A potassium ion is bound to the N atoms of the thiazole rings (K(1).N(1), 2.47(2) Å; K(1).N(5), 2.50(2) Å) and to the adjacent O (amide) atoms (K(1).O(1), 2.34(1) Å; K(1).O(5), 2.34(1) Å). Two perchlorate anions, located on either side of the plane of the macrocyclic ring, are weakly associated with the potassium cation (K(1).O(10), 2.72(3) Å; K(1).O(16), 2.48(3) Å). This cyclic octapeptide reacts with copper(II) to give a purple solution (lambda(max) 590 nm).

Cyclic peptide marine metabolites and CuII

“…7). 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.…”

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].…”

Effects of amino acids and chirality for molecular folding of desoxazoline-ascidiacyclamide derivatives: X-ray crystal structures of four cyclic octapeptides including unusual amino acids,cyclo(-Ile-aThr-D-Val-Thz-)2,cyclo(-Ala-aThr-D-Val-Thz-Ile-aThr-D-Val-Thz-),cyclo(-Val-aThr-D-Val-Thz-Ile-aThr-D-Val-Thz-), andcyclo(-Ile-aThr-Val-Thz-Ile-aThr-D-Val-Thz-)

“…We are also interested in such flexible conformers to consider the control of molecular folding. Indeed, the desoxazoline‐ascidiacyclamide [(DOASC), 1 = cyclo (–Ile– a Thr– D ‐Val–Thz–) 2 ], which lacks the Oxz blocks of ASC, resulted in the novel pseudoboat or pseudochair form in solution ( a Thr, L ‐ allo ‐threonine) 11–13. Furthermore, the relationships between DOASC and the accumulation of certain metals in marine organisms have been proposed 14–16.…”

“…Furthermore, the relationships between DOASC and the accumulation of certain metals in marine organisms have been proposed 14–16. Their metal complexes17, 18 are also interesting in controlling the conformation.…”