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24 June 1988 Membrane Interactions Of The Anthracycline Antibiotics
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Proceedings Volume 0909, Time-Resolved Laser Spectroscopy in Biochemistry; (1988) https://doi.org/10.1117/12.945426
Event: 1988 Los Angeles Symposium: O-E/LASE '88, 1988, Los Angeles, CA, United States
Abstract
The intrinsic fluorescence properties of the anthracycline antitumor antibiotics were exploited here to study the manner in which a 14-valerate substituent modulated relative drug location and dynamics in fluid-phase bilayers at 37°C. Using Adriamycin (A), N,N-dimethyladriamycin (NDA), N-trifluoroacetyladriamycin (NTA), N-benzyladriamycin (NBA), and their corresponding valerate-substituted analogs (AD48, AD199, AD32 and AD198, respectively), the accessibilities of bound fluorophores to membrane-impermeable iodide were evaluated in quenching experiments conducted at constant ionic strength, while the diffusive motions of these agents were studied through the use of lifetime-resolved anisotropy plots. Incorporation of a bulky 14-valerate side chain into an anthracycline was found to enhance the hindered rotations experienced by a bound drug molecule, with limiting anisotropy (a.) values increasing from 0.166 to 0.258 for NTA and from 0 243 to 1 0.264 for NBA. However, the bimolecular quenching rate constants (x10 M ls ) for membrane-bound A (1.4), AD48 (1.1), NDA (1.8), AD199 (1.1), NBA (0.8), AD198 (0.7), NTA (0.4) and AD32 (0.5) indicate that the hydrophobic side chain was not, in general, a strong modulator of fluorophore penetration into the bilayer.
© (1988) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.
Thomas G Burke, James H Doroshow, and Thomas R Tritton "Membrane Interactions Of The Anthracycline Antibiotics", Proc. SPIE 0909, Time-Resolved Laser Spectroscopy in Biochemistry, (24 June 1988); doi: 10.1117/12.945426; https://doi.org/10.1117/12.945426
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