Isolation of dolastatins 10–15 from the marine mollusc

Isolation and Structure Determination of Lyngbyastatin 3, a Lyngbyastatin 1 Homologue from the Marine Cyanobacterium Lyngbya majuscula. Determination of the Configuration of the 4-Amino-2,2-dimethyl-3-oxopentanoic Acid Unit in Majusculamide C, Dolastatin 12, Lyngbyastatin 1, and Lyngbyastatin 3 from Cyanobacteria

“…These physical characteristics suggested that 1 was related to the known L. majuscula metabolite lyngbyastatin 1 (2). While the IR, UV, and J H NMR spectra of 1 and 2 were virtually identical, a comparison of the two samples by reversed-phase HPLC 15 indicated that 1 was more lipophilic than 2.…”

“…These results indicate that our cyanobacterial samples of dolastatin 12 and lyngbyastatin 1 and 3 are mixtures of two Ibu epimers. The configuration of the major Ibu epimer in each of the three mixtures is R. The relative amounts of the two epimers, as determined by HPLC analysis after borohydride reduction, was 4:1 for both lyngbyastatin 1 (2) and dolastatin 12 (3), but 2:1 for lyngbyastatin 3 (1). The samples of 2 and 3 had both been isolated from the same collection of L. majuscula, but the sample of lyngbyastatin 3 (1) had been obtained from several different collections of L. majuscula from Apra Harbor.…”

“…The stereochemical differences in the Ibu units of the compounds isolated from cyanobacteria and sea hares may be caused by epimerization of the R to the thermodynamically favorable S-Ibu configuration that occurred either in the digestive gut of the sea hare or perhaps during the isolation of the sea hare metabolites. 2 However, a simpler explanation is that the cyanobacterium eaten by the sea hare produces dolastatin 12 with only the (S)-Ibu unit, analogous to what is found in majusuclamide C.…”

“…In 1998, we reported the isolation and biological evaluation of samples of lyngbyastatin 1 (2) and dolastatin 12 (3) from a Lyngbya majuscula I Schizothrix calcicola assemblage. 5 The structure determinations of these cyanobacterial samples were hampered by the extensive signal doubling and broadening observed in the NMR spectra, a phenomenon not seen in the NMR spectra of majusculamide C (4) 7d from cyanobacteria or the samples of dolastatin 11 (5) 8 and dolastatin 12 (3) 8 from the sea hare.…”

Rapid Optimization of a Peptide Inhibitor of Malaria Parasite Invasion by Comprehensive N-Methyl Scanning

“…Additionally, it results in a loss of hydrogen bonding potential at the affected site, reducing the role of mainchain hydrogen bonds at a binding interface and potentially altering binding properties (17). There are a number of examples of N-methyl amino acid containing peptides with a range of bioactivities, including antibiotic (18), anti-viral (19), anti-cancer (20), and immunosuppressant activities (21). Importantly, modification of biologically active peptides by the inclusion of N-methyl amino acids into an original sequence has been shown to enhance the potency (22), change the receptor subtype selectivity (23), and stabilize a peptide toward proteolytic degradation in a biological system (24).…”