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Interaction of an Endosomolytic Polyamidoamine ISA23 with Vesicles Mimicking Intracellular Membranes: A SANS/EPR Study
Authors:Peter C. Griffiths  Renuka Nilmini  Emma Carter  Patrick Dodds  Damien M. Murphy  Zeena Khayat  Ettore Lattanzio  Paolo Ferruti  Richard K. Heenan  Stephen M. King  Ruth Duncan
Affiliation:1. School of Chemistry, Cardiff University, Main Building, Park Place, Cardiff CF10 3AT, UK;2. Center for Polymer Therapeutics, Welsh School of Pharmacy, Redwood Building, King Edward's VII Avenue, Cardiff CF10 3XF, UK;3. Dipartimento di Chimica Organica e Industriale, Universita di Milano, Via Venezian 21, 20133 Milano, Italy;4. ISIS facility, STFC, Rutherford Appleton Laboratory, Didcot OX11 0QX, UK
Abstract:The mechanism of ISA23 · HCl interaction with model membrane vesicles (80–100 nm in diameter) was investigated using EPR in conjunction with SANS. For EPR, 16‐DSE was dissolved in the vesicle membrane to measure its dynamics and polarity, whereas a spin‐labeled (Tempo)‐ISA 23 analogue was used to give a measure of the polymer flexibility. When ISA23 was added to the external vesicle surface, no interaction was found. This observation conflicts with the reported ability to lyse RBC, but is in agreement with recent studies that showed no effect on membrane permeability when a PAA was added to an incubation medium containing isolated lysosomal vesicles. The vesicle‐mimetic models used here provide a new and useful tool for studying endosomolytic polymer/membrane interactions.
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Keywords:electron spin resonance  endosomolytic polymers  membranes  polymer/surface interactions  spin labels
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