Aselacins, novel compounds that inhibit binding of endothelin to its receptor. II. Isolation and elucidation of structures

• Published in: Journal of antibiotics Vol. 47; no. 5; p. 528
• Main Authors: Hochlowski, J E, Hill, P, Whittern, D N, Scherr, M H, Rasmussen, R R, Dorwin, S A, McAlpine, J B
• Format: Journal Article
• Language: English
• Published: Japan 1994
• Subjects: Acremonium - chemistry; Amino Acid Sequence; Amino Acids - analysis; Chromatography, High Pressure Liquid; Endothelin Receptor Antagonists; Indoles - chemistry; Indoles - isolation & purification; Magnetic Resonance Spectroscopy; Molecular Sequence Data; Molecular Structure; Peptides, Cyclic - chemistry; Peptides, Cyclic - isolation & purification
• ISSN: 0021-8820
• DOI: 10.7164/antibiotics.47.528

Three novel compounds, named the aselacins, which inhibit the binding of endothelin to its receptor have been isolated from two related Acremonium species of fungi grown in stationary culture. These compounds are cyclic pentapeptolides with a ring formed by cyclo[Gly-D-Ser-D-Trp-beta-Ala-L-Thr] and an additional exocyclic D-Gln to which is attached a functionalized long chain fatty acid. The aselacins differ in the functionalization of this acid. The structures of the aselacins were determined by amino acid analysis, mass spectrometry and evaluation of 1-D and 2-D homonuclear and heteronuclear 1H, 13C and 15N NMR spectra in protic and aprotic solvents. The stereochemistry of the amino acids present was elucidated by chiral HPLC of hydrolyzed compound.