Patellamides

Didemnin B (347) is a cyclic depsipeptide isolated from the Caribbean tunicate Trididemnum solidum and is currently in phase II clinical trials as an anticancer agent. Didemnin B also shows antiviral and immunosuppressive activity. The structure of didemnin B was revised to 347 containing 

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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...

Williams, A.B. and Jacobs, R.S. (1993) A marine natural product, patellamide D, reverses multidrug resistance in a human leukemic cell line. Cancer Letters, 71, 97. 

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. 

Wadleigh RW, Yu SJ (1988) Detoxification of iso thiocyanate allelochemicals by glutathione transferase in three lepidopterous species. J Chem Ecol 14 1279-1288 Werck-Reichhart D, Feyereisen R (2000) Cytochromes P450 a success story. Genome Biol 1 1-9 Williams AB, Jacobs RS (1993) A marine natural product, patellamide D, reverses multidrug resistance in a human leukemic cell line. Cancer Lett 71 97-102 Yazaki K (2006) ABC transporters involved in the transport of plant secondary metabolites. FEBS Lett 580 1183-1191... 

Lissoclinum species of tunicates produce a range of cyclic peptides, which contain thiazole, thiazoline and oxazoline rings. Most belong to the general families patellamides (octapeptides), lissoclinamides (heptapeptides) or bistratamides (hexapeptides) [22],... 

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],... 

Three cytotoxic peptides, patellamide D (31) and lissoclinamides 4-5 (32-33) were isolated from a Great Barrier Reef specimen of L. patella and identified by interpretation of spectral data. The peptides were found within the obligate algal symbiont of the genus Prochloron [65]. Another study of the same Australian L. patella reported lissoclinamide 6 (34), in addition to lissoclinamides 4-5 (32-33) and patellamide D (31). The structure of patellamide D (31) was obtained by X-ray crystallography and its conformation compared with those obtained by molecular modelling [66]. Patellamide D (31) has been reported to be a... 

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]. 

Although historically most useful antibiotics have come from spore forming microorganisms, marine organisms have yielded the candidate antitumor peptide dideinnin B and cytostatic peptides such as the patellamides. Many of the marine peptides have little or no antimicrobial... 

A mixture of polyandrocarpidine metabolites 15 3—156 from the ascidian Polyandrocarpa sp. deters feeding by hermit crabs and two species of snails.28 Nitrogenous ascidian compounds that are reported to lack antifeedant effects include patellamide C (Lissochnurn patella),28 and eudistomins G and H.176... 

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