Unit:
Κατεύθυνση ΦυσικοχημείαLibrary of the School of Science
Author:
Χατζηγεωργίου Πέτρος
Dissertation committee:
Βύρας Κυριάκος Καθηγ.(Επιβλέπων), Μαυρομούστακος Θωμάς Καθηγ., Τσεκούρας Αθανάσιος Επικ. Καθηγ.
Original Title:
Φυσικοχημική μελέτη αλληλεπιδράσεων βιοδραστικών μορίων σε λιπιδικές μεμβράνες
Summary:
In the past, lipid bilayers were only thought as static entities and served
mainly as barriers for the toxic substances. Today, it is well recognized that
they are dynamic structures that play an important role in determining drug
action. A new scientific field named lipidomics cavers this aspect. Based on
this concept, we sought to examine the role of lipid bilayers for the
amphiphilic molecules vinblastine and vincristine which are proposed to act on
the membrane lipid bilayer. It has also been proposed that each membrane
perturbing drug has its own fingerprint and this may determine its
pharmacological effects. For this reason, we found it very interesting to study
the membrane interactions of vinblastine and vincristine and made an effort to
correlate their fingerprint and pharmacological action.
To achieve this aim we investigated the interactions caused by the insertion
of Vinca alkaloids vinblastine and vincristine in lipid bilayers of
dipalmitoylphospatidylocholine (DPPC), by using the physicochemical techniques
of Differential Scanning Calorimetry (DSC) and Raman Spectroscopy. In addition,
we studied the effect of this two pharmaceutical molecules with the presence of
cholesterol.
The thorough analysis of the obtained results point out that: a) the insertion
of Vinca alkaloids in lipid bilayers causes partial interdigitation of
aliphatic chains, a phenomenon which influences the biological activity of
these molecules; b) the incorporation of this pair of molecules results in the
creation of various and distinct domains attributed to their different
developed interactions; c) after their localization in membrane bilayers they
exhibit similarities and differences in terms of synergistic effect with the
bioactive molecule of cholesterol.
Keywords:
Interdigitation, Vinblastine, Vincristine, Differential scanning calorimetry, Raman spectroscopy
Number of index pages:
1-9
