104883-49-0Relevant articles and documents
Total structure and inhibition of tumor cell proliferation of laxaphycins
Bonnard, Isabelle,Rolland, Marc,Salmon, Jean-Marie,Debiton, Eric,Barthomeuf, Chantal,Banaigs, Bernard
, p. 1266 - 1279 (2007/10/03)
From a mixed assemblage of Lyngbya majuscula rich marine cyanobacteria, we isolated a series of cell growth inhibitory cyclic peptides, The structures of the two major components, laxaphycins A (1) and B (2), and of two minor peptides, laxaphycins B2 (3) and B3 (4), were determined by spectroscopic methods and degradative analysis. Absolute configurations of natural and nonproteinogenic amino acids were determined by a combination of hydrolysis, synthesis of noncommercial residues, chemical derivatization, and HPLC analysis. The organism producing the laxaphycins was identified as the cyanobacterium Anabaena torulosa. The antiproliferative activity of laxaphycins was investigated on a panel of solid and lymphoblastic cancer cells. Our results demonstrate that in contrast to laxaphycin A, laxaphycin B inhibits the proliferation of sensitive and resistant human cancer cell lines and that this activity is strongly increased in the presence of laxaphycin A. This effect appears to be due to an unusual biological synergism.
Total structure of hormothamnin A, a toxic cyclic undecapeptide from the tropical marine cyanobacterium hormothamnion enteromorphoides
Gerwick, William H.,Jiang, Zhi D.,Agarwal, Santosh K.,Farmer, Bennett T.
, p. 2313 - 2324 (2007/10/02)
The tropical marine cyanobacterium Hormothamnion enteromorphoides produces a suite of cytotoxic and antimicrobial cyclic peptides. The structure of the most lipophilic of these, hormothamnin A, was determined by interpretation of physical data, principally high NMR and FAB MS, in combination with chemical derivitization and degradation schemes. Isolation of a key pentapeptide fragment DPHE-D-LEU-L-ILE-D-allo-ILE-L-LEU, obtained under partial hydrolysis conditions, was instrumental to the final structure determination. β-D-aminooctanoic acid (D-BAOA) was characterized as a per-ester derivative following complete acid hydrolysis and Z-didehydrohomoalanine (DHHA) was spectroscopically in the intact peptide. The remaining residues (HYPRO, 2 × HSER, GLY) were evident from amino acid and spectroscopic analysis. Sequencing of these residues made use of knowledge from fragments, high field NMR (NOESY and ROESY) and FAB MS analysis of the intact peptide. Absolute stereochemistries of the α-amino residues were determined by HPLC analysis of the acid liberated residues derivatized with Marfey's reagent. The absolute stereochemistry of the β-amino residue was shown by circular dichoroism analysis, HPLC analysis of the Marfey derivative, and chiral synthesis of a homolog. By these techniques, hormothamnin A was demonstrated to possess a cyclo-[D-PHE-D-LEU-L-ILE-D-allo-ILE-L-LEU-GLY-D-BAOA-L-HSER-DHHAL-HYPRO-L-HSER] structure.
