Patellamide A

Schmidt, E.W., Nelson, J.T., Rasko, D.A. et al. (2005) Patellamide A and C biosynthesis by a microcin-like pathway in Prochloron didemni, the cyanobacterial symbiont of Lissoclinum patella. Proceedings of the National Academy of Sciences of the United States of America, 102, 7315. 

Three cyclic octapeptides, patellamides A-C (21-23) were isolated from L. patella and cytotoxicity data for these compounds and for ulicyclamide (15) and ulithiacyclamide (16) against L1210 murine leukaemia cells and the human acute lymphoblastic leukaemia (ALL) cell line CEM were reported [52]. The structures of the patellamides were later reassigned on the basis of synthetic studies. The proposed structures of patellamides B (22) and C (23) were synthesised and the products were shown to differ from the natural products. This led to new structures being proposed [53,54]. Separate syntheses of... 

The spectral data of the patellamides was also reasssigned and the new assignments used for elucidation of the structures of three new metabolites, the octapeptide prepatellamide B formate (24) and the heptapeptides, prelissoclinamide 2 (25), and preulicyclamide (26) [58]. The molecular conformation of patellamide A (21) was determined by X-ray crystallography [59,60] and the solution conformations of patellamides B (22) and C (23) were determined by NMR spectroscopy and molecular dynamics [61]. The octapeptide preulithiacyclamide (27) is a potent inhibitor of Macrophage Scavenger Receptor and was isolated from L. patella from Palau along with other known cyclic peptides [62],... 

Schmidt EW, Nelson JT, Rasko DA, Sudek S, Eisen JA, Haygood MG, Ravel J (2005) Patellamide A and C Biosynthesis by a Microcin-like Pathway in Prochloron didemni, the Cyanobacterial Symbiont of Lissoclinum patella. Proc Natl Acad Sci USA 102 7315... 

Schmidt EW, et al. Patellamide A and C biosynthesis by a microcin-hke pathway in Prochloron didemni, the cyanobacterial... 

Figure 5. CD spectra of patellamide A at 0.2 mg/mL in methanol plus 2 eq. of zinc and...

Calculation of the binding constants for patellamide A (1) was quite straightforward as only three sequential states had to be considered. These were unbound, singly bound and doubly bound and it was assumed that this took place in the manner shown below and that there was no difference in the two binding sites available. Although deprotonation of the peptide occurs prior to inclusion of the metal at each step, as shown in equations 1-3 (2" deprotonation not included), this could not be incorporated into the calculation as there are no deprotonation constants for amides available. ... 

Table 2. Binding constants of patellamide A and C with copper and zinc...

This would lead us to expect selectivity for copper over zinc as observed as well as preferential binding to copper over nickel. It must be noted that the symmetrical patellamide A is non-selective for Cu, even though the Irving-Williams series would... 

MASS SPECTROMETRIC STUDIES OF THE METAL BINDING OF PATELLAMIDE A AND C... 

Table 6. Main species detected in the MS of patellamide A plus 2eg. Cu solution...

The competition experiments with patellamide A produced mixed species in each case with some zinc only, some copper only and some copper/zinc doubly charged complexes. The peaks in the spectra for copper only species were of slightly greater intensity suggesting a small preference for copper but not on the scale of that displayed by patellamide C. These results agreed with those obtained by CD where a hybrid copper/zinc spectrum was obtained in the presence of both metals. Further evidence came from the HRMS of a solution of patellamide A to which a mixture of copper and... 

As an additional experiment, a 1 1 mixture of patellamides A and C was made up in methanol and to this was added 1 eq, of copper. The resulting spectrum showed as the 100% peak [PatAHs + Cu]" at m/z 805. The patellamide C was mainly in the form of [PatCH4 + Na]" at m/z 785. This would suggest that patellamide A can out-compete patellamide C for copper, but further experiments would be necessary to confirm this. 

The formation of the CU2CI complex of patellamide A became constant after the addition of 1 equivalent of copper suggesting that although two coppers could be bound by patellamide A this complex was much less stable than the single copper complex or the 2Cu complex formed by patellamide C. The formation of the [PatAHs + Cu]" complex of patellamide A was very clear with the intensity of that species reaching a maximum after the addition of one equivalent of the metal and remaining constant thereafter. 

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