Structure of the novel steroidal antibiotic squalamine determined by two-dimensional NMR spectroscopy.
Squalamine is a novel aminosterol recently isolated from the dogfish shark, Squalus acanthias. This water-soluble steroid exhibits potent antibacterial activity against both gram-negative and gram-positive bacteria. In addition, squalamine is fungicidal and induces osmotic lysis of protozoa. We report here the structural determination of squalamine, 3 beta-N-1-[N(3-[4-aminobutyl])-1,3 diaminopropane]-7 alpha,24 zeta-dihydroxy-5 alpha-cholestane 24-sulfate, which was deduced from the analysis of fast atom bombardment spectra and a series of two-dimensional nuclear magnetic resonance (NMR) spectra. Squalamine is a cationic steroid characterized by a condensation of an anionic bile salt intermediate with the polyamine, spermidine. This molecule is a potential host-defense agent in the shark, and provides insight into a new class of vertebrate antimicrobial molecules.
Wehrli
S L
SL
Division of Biochemical Development and Molecular Disease, Children's Hospital of Philadelphia, Pennsylvania.
Moore
K S
KS
Roder
H
H
Durell
S
S
Zasloff
M
M
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification; D001647:Bile Acids and Salts / Q000737:chemistry; D002777:Cholestanols / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification; D002851:Chromatography, High Pressure Liquid; D004284:Dogfish; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013095:Spermidine / Q000737:chemistry; D013431:Sulfates / Q000737:chemistry
D000900:Anti-Bacterial Agents; D001647:Bile Acids and Salts; D002777:Cholestanols; D013431:Sulfates; C079655:squalamine; D013095:Spermidine