Antineoplastic cyclic peptides from the marine tunicate Lissoclinum patella

Abstract

Pak B with 5% E^O in hexane at 2 mL/min as the eluant and with the UV detector at 350 nm. The retention data are shown in Table VI. The solvents were from Burdick and Jackson, and they were degassed prior to use. Nuclear Overhauser Effect (NOE) Determinations. AllNOEs were measured on a Bruker WM-250 spectrophotometer operating in the pulse-FT mode. Each sample (ca. 5 mg) was dissolved in 0.5 mL of dry deuterioacetone (Merck acetone-d6 "100% "), degassed by several freeze-pump-thaw cycles and sealed.The NOE values were determined from the ratio between the relative peak intensities with the irradiating field on resonance and off resonance for the saturated signal. At least five NOE measurements were made for each signal of each sample studied. The standard deviation was always 2% or less. The field strength of the irradiating field was determined for each sample by setting the decoupling power level so that a maximum increase in intensity of interacting protons was obtained without affecting other proton signals. In all experiments the pulse delay time used was sufficiently long to allow complete recovery of all signals. This time ranged from 40 to 60 s, depending on the sample. The ambient probe temperature was 24 °C; the high-temperature experiments were run at 50 °C and the low temperature experiments at -50 °C. No significant changes were observed in the spectra or the NOE values at either the high or low temperatures.Acknowledgment. This work was supported in part by National Cancer Institute Contract No. N01-CP-75932.

Patellamide A and C biosynthesis by a microcin-like pathway inProchloron didemni, the cyanobacterial symbiont ofLissoclinum patella

“…We previously reported that the reef sample contained patellamides A and C (29) in nearly equimolar amounts. Other patellamides were not detected as major products in the crude extract.…”

Patellamide A, a cytotoxic cyclic peptide from the ascidian Lissoclinum patella

“…As part of a series of studies on the relationship between the chemical structural symmetry and the molecular conformation in cyclic peptides from marine ascidian, the crystal structure of patellamide A (1), a cytotoxic cyclic peptide from Lissoclinum patella (Ireland, Durso, Newman & Hacker, 1982) was determined by X-ray single-crystal analysis. The conformational analysis of this molecule, which has a non-C2-symmetric methyl group on one side of two C2-symmetric dihydro oxazole rings, appears to be important in considering the ~active conformation' of cytotoxic cyclic peptides from ascidian, as seen from the C2-symmetric ascidiacyclamide (2) which takes a rectangular conformation (Ishida, Tanaka, Nabae, Inoue, Kato, Hamada & Shioiri, 1988;Ishida, In, Doi, Inoue, Hamada & Shioiri, 1992).…”

A global assembly line for cyanobactins

“…Patellamide-containing ascidians harbor cyanobacterial symbionts, Prochloron spp., that have eluded cultivation. Recently, it was shown that Prochloron didemni is responsible for synthesizing cyclic peptides 2,3 that were originally isolated from the host ascidians 4,5 . Surprisingly, single point mutations in short cassettes in the biosynthetic gene clusters resulted in a diverse product library 6 .…”

“…The patellamides (3)(4)(5)(6)(7)(8) are biosynthesized through a unique ribosomal route 2 with some similarity to microcin pathways ( Fig. 1) 8 .…”