Two distinct conformers of the cyclic heptapeptide phakellistatin 2 isolated from the fijian marine sponge stylotellaaurantium.
The isolation, structure determination, and solution conformation of two conformers of the cyclic heptapeptide phakellistatin 2 (cyclo-[Phe1-cis-Pro2-Ile3-Ile4-cis-Pro5-Tyr6-cis-Pro7]) isolated from the Fijian marine sponge Stylotella aurantium are reported. The conformers can be isolated separately by HPLC and are stable in methanol solution over a period of weeks as determined by NMR. Their NMR spectra and mass spectral fragmentation patterns differ significantly. Their solution conformations were determined by NOE-restrained molecular dynamics calculations and indicated that the two conformers had different folds, hydrogen bonding patterns, and solvent accessible surfaces. These factors may contribute to the independent stability of the two conformers, and may explain the variable biological activity previously reported for phakellistatin 2.
Tabudravu
Jioji N
JN
Marine Natural Products Laboratory, Department of Chemistry, University of Aberdeen, Old Aberdeen, Scotland, UK.
Jaspars
Marcel
M
Morris
Linda A
LA
Kettenes-Van Den Bosch
J Jantina
JJ
Smith
Nigel
N
D000595:Amino Acid Sequence; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004354:Drug Screening Assays, Antitumor; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D005367:Fiji; D006801:Humans; D020128:Inhibitory Concentration 50; D007951:Leukemia, Myeloid; D010051:Ovarian Neoplasms; D010456:Peptides, Cyclic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D011161:Porifera / Q000737:chemistry*; D011487:Protein Conformation; D013237:Stereoisomerism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D010456:Peptides, Cyclic; C119157:phakellistatin 2