There is a need for biocompatible, biodegradable, 3-D printable and stable hydrogels especially in the areas of tissue engineering, drug delivery, bio-sensing technologies and antimicrobial coatings. The main aim of this Ph.D. work was to fabricate polypeptide based hydrogel which may find a potential application in those fields. Focusing on tyrosine or tryptophan-containing copolypeptides prepared by NCarboxyanhydride (NCA) polymerizations, three different crosslinking strategies have been tested to obtain polypeptide hydrogels.
1- Enzymatic crosslinking of tyrosine (Chapter 2): Horseradish peroxidase (HRP) enzyme crosslinks tyrosine via a radical formation mechanism. There are several reports of HRP crosslinked tyramine modified natural polymers such as chitosan, hyaluronic acid. However, when a library of tyrosine containing synthetic polypeptides was tested for HRP crosslinking, none of resulted in gel formation.
2- TAD click crosslinking of tyrosine (Chapter 3): 4-Phenyl-1,2,4-triazole-3,5-dione reacts (PTAD) with tyrosine in a click-like manner.1 Tyrosine copolypeptides were successfully reacted with commercially available PTAD. Then, a series of monofunctional and bifunctional TAD compounds were synthesized and tested. Hydrogels were obtained by crosslinking copolypeptides with hexamethylene-bisTAD. Although TAD-tyrosine reaction is fast and selective, TADs’ instability in aqueous conditions is a limitation for this system.
3- TAD click crosslinking of tryptophan (Chapter 4): Methyl-TAD reacts with indole groups very fast, efficiently and reversibly in organic solvents.2 Tryptophan (indole-containing amino acid) NCA monomer was synthesized, characterized and copolymerized with PEG-amine, Z-Lys, and BLG NCAs. Novel mono and bifunctional PEG-TADs were also synthesized. The polypeptides were PEGylated and crosslinked to produce hydrogels.
4- Novel organohydrogels (Chapter 5): The successfull strategy from Chapter 4 was further applied to produce novel organohydrogels gels with defined segments. Control over gelation kinetics was demonstrated by the hexamethylene-bisTAD reaction with tryptophan containing copolypeptides. Applying controlled lysine and glutamic acid deprotection, non-toxic organohydrogel consisting of a hydrophobic core and a hydrophilic shell were obtained.
Item Type:
Thesis (PhD)
Date of Award:
January 2018
Refereed:
No
Supervisor(s):
Heise, Andreas
Uncontrolled Keywords:
tyrosine; tryptophan; Novel organohydrogels; Enzymatic crosslinking; TAD click crosslinking