Unit:
Κατεύθυνση Επιστήμη Πολυμερών και Εφαρμογές τηςLibrary of the School of Science
Author:
Σκουλάς Δημήτριος
Supervisors info:
Ιατρού Ερμόλαος Αναπλ. Καθηγητής ΕΚΠΑ (επιβλέπων), Πιτσικάλης Μαρίνος Αναπλ. Καθηγητής ΕΚΠΑ, Σακελλαρίου Γεώργιος Αναπλ. Καθηγητής ΕΚΠΑ
Original Title:
Σύνθεση συμπολυμερών πολυαιθυλενοξειδίου και ιστιδίνης με γ-βενζυλεστέρα του γλουταμικού οξέος και επίδραση του εστέρα στο pKa της πολυιστιδίνης
Translated title:
Synthesis of block polymers polyethylenoxide and histidine with γ-benzylester of glutamic acid and influence of the ester to pKa of polyhistidine
Summary:
The purpose of this thesis is the synthesis of diblocks containing L-Histidine,
which will be used for the selective and controlled delivery of anticancer
drugs. It is presented a novel method for the synthesis of Nim-Trt-L-Histidine
NCA with Trityl protecting group, which gives the advantages of selective and
easy deprotection and no racemization. Also the synthesis of γ-Βz-L-Glutamate
NCA took place. The successful synthesis of the monomers was confirmed with IR
and NMR techniques. The successful synthesis of the poly(L-histidine), of a
diblock with m-PEO and co-diblocks with addition of PBLG in rates of 10%, 20%
and 40% in relation with histidine in the second block of the polymers took
place beginning with m-PEO-NH2 as macroinitiator in the first block. The ROP
method for the polymerization of the NCAs of the aminoacids took place in
combination with the use of high vacuum techniques. All polymers were
characterized with GPC, NMR and IR techniques.
The polymers have the ability of self-assembly by shaping in nanoscale micelles
and clusters in water as solvent. Because of the self-assembly, they can
deliver drugs. This ability was confirmed with DLS. These polypeptides can
respond in pH change, an ability in which the selective release of the drug is
based on. The pKa of poly(L-histidine) was found between 6.65 and 6.7 with UV
titrations. Moreover titrations by weight have shown that we have increase of
the Ka of the diblocks, when we have increase in the rate of the PBLG. A study
of the secondary structure of the poly(L-histidine) took place by using
circular dichroism. The different molds of the polymer were found by changing
pH and temperature.
Keywords:
Polypeptides, NCA, Self-assembly, Drug delivery, Bioapplications
Number of index pages:
15-16, 18-20, 22
