Ulithiacyclamides

Figure 11.6 The patE gene in the patellamide biosynthetic gene cluster encodes the peptide precursor (sequence in rectangle box) of patellamide C and ulithiacyclamide. Substitution of the precursor cassette for ulithiacyclamide with an artificial cassette (sequence in ellipse region) resulted in the biosynthesis of a new unnatural peptide, eptidemnamide...

The heptapeptide ulicyclamide (15) and the octapeptide ulithiacyclamide (16) were the first representatives of a series of cyclic peptides to be isolated from Lissoclinum patella. Their structures were elucidated by interpretation of spectral data [44], A revised structure was later put forward for ulicyclamide (15) as a result of a detailed analysis of the fast atom bombardment (FAB) mass spectrum. The same paper reported the isolation of two more polar cyclic peptides and another, which was present as a minor component. These heptapeptides were called lissoclinamides 1-3 (17-19) [45]. An unidentified tunicate from the Great Barrier Reef contained ulithiacyclamide (16) and ascidiacyclamide (14) [46]. Two syntheses of ulithiacyclamide (16)... 

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... 

A further cytotoxic, octapeptide, patellamide E (40), was isolated from L patella from Singapore and the structure was elucidated by chemical and spectral methods [75]. Patellamide F (41) was isolated from L. patella from north-western Australia and was also cytotoxic. The structure and absolute stereochemistry of patellamide F (41) were established by chemical and spectroscopic methods. Patellamide B (22), ulithiacyclamide (16) and lissoclinamide 3 (19) were also isolated from the same sample [76]. The octapeptides, patellamide G (42) and ulithiacyclamides E-G (43-45) were isolated from L. patella from Pohnpei, along with known series members [77]. 

Two cyclic peptides that were isolated from the marine tunicate Lissoclinum patella,30 named ulicyclamide and ulithiacyclamide, have structures (33) and (34). 

As previously stated, these cyclic peptides have shown significant bioactivity in different screening regimes and a strong structure-activity relationship has been noted by several workers, with the disulphide bridge in the ulithiacyclamides e.g. 17,18) making these the most cytotoxic of the compounds isolated from L. Patella. It is thought that the... 

Further four new cyclic thiazole peptides, patellamide G (404, a novel immunosuppressant), ulithiacyclamides E 405, F 406 and G 407, were isolated from the ascidian L. patella <1998JNP1547, 1998JA12237>. 

Cys is nearly always heterocyclized with the sole exception of the ulithiacyclamide group, in which two of the four Cys residues form a disulfide bridge and the other two are thiazole heterocycles. 

Table references aerucyclamide ascidiacyclamide, lissoclinamide, patellamide, and ulithiacyclamide group ... 

Most of the work on metal-binding cyanobactins has focused on Cu(II) and Zn(II) binding with the patellamides. Patellamides A, B, C, D, and E, as well as ulithiacyclamide, have been shown to bind Cu(II) and Strikingly, patellamide C was shown to selectively bind Cu(II) even in the presence of... 

---