Patellamide, B and

The conformation in solution of the important thiazole-containing hexapeptides Patellamides B and C (see Section 3.06.11) have been determined by NMR spectroscopy and molecular dynamics <95JOC3944>. 

Most other cytotoxin cyanobactins are active in the clinically irrelevant micromolar range. However, their MDR profiles may be of interest nonetheless. Patellamide D was the first example of this activity, and the molecule was shown to be a selective antagonist to MDR, improving the potency of certain drugs in human cell lines. Dendroamides and patellamides B and C were later shown to have similar properties. ... 

Patellamides B and C, Cytotoxic Cyclic Peptides from a Tunicate. 2. Their Real Structures have been Determined by Their Syntheses. Tetrahedron Lett. 26, 5159 (1985). 

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. 

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],... 

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... 

Lissoclinum bistratum contains mostly cyclic hexapepti-des/ but Lissoclinum patella has yielded patellamides A-G (Figure 28.15), which are regarded as octapeptides, as well as ulithiacyclamides A and B and pre-ulithiacydamide these last three peptides are characterized by the presence of an intracyclic disulfide bridge. Lissoclinum patella has also yielded asddiacydamide, which had been isolated in 1983 from an tmdetermined ascidian, and tawicyclamides A and which appear to be currently the only cyclic peptides containing only thiazoles or thiazolines. These... 

In a study of Lissodinum patella harvested in Palau, patellamides A, B and C were not present in the Prochloron sp. symbionts but were scattered in the tunic of the ascidian (Salomon and Faulkner, 2002 Piel, 2004). Later, genetic studies established that patellamides A and C were produced by symbiotic Prochloron (Prochloron didemni) that were isolated from the ascidian and were shown to contain the necessary genes for the formerly considered non-ribosomal but, actually, post-translationally modified ribo-somal biosynthesis of these peptides (Schmidt, Sudek, and Haygood, 2004 Schmidt et al., 2005 Milne et al., 2006 Oman and van der Donk, 2010). 

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... 

Although historically most useful antibiotics have come from spore forming microorganisms, marine organisms have yielded the candidate antitumor peptide didemnin B [77327-50-0] (2) and cytostatic peptides such as the patellamides (3). Many of the marine peptides have little or no antimicrobial activity. Antibacterial peptides called magainins are found in frog skin (4) and antibacterial proteins called defensins are found in mammalian white blood cells (5). The commercially important insecticidal proteins from Bacillus thuringensis (6) are not discussed herein nor are the numerous peptide siderophores (7,8), which, except for the albomycins (9), are usually not antimicrobial. 

Michibata, H., Terada, T., Anada, N., Yamakawa, K., and Numakunai, T. (1986a) The accumulation and distribution of vanadium, iron and manganese in some solitary asddians. Biol. Bull., 171, 672-681. Milne, B.F., Long, P.F., Starcevic, A., Hranueli, D., and Jaspars, M. (2006) Spontaneity in the patellamides biosynthetic pathway. Org. Biomol. Chem., 4, 631-638. 

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