Konstanze K. Julich-Gruner

Synthesis and characterization of oligo(ethylene glycol)s functionalized with desaminotyrosine or desaminotyrosyltyrosine

Purpose The aromatic compounds desaminotyrosine (DAT) and desaminotyrosyltyrosine (DATT) have been successfully used to functionalize gelatin in order to form physically crosslinked networks via p-p interactions and hydrogen bonds of the introduced phenol moieties. Here, it was explored whether this concept can be applied to a synthetic polymer not engaging in additional interactions such as triple helix formation in gelatin, enabling a network to form by physical interactions mainly related to the terminal functional groups. Oligo(ethylene glycol) (OEG) was chosen as hydrophilic synthetic polymer for the backbone structure. Methods Linear OEG (MP = 3 kDa) and four-arm OEG (Mn = 5 kDa) with amino functionalities as endgroups were functionalized with DAT and DATT using EDC·HCl and NHS as activating agents. The compounds were characterized by NMR, IR spectroscopy, and MALDI. Rheological behavior of aqueous solutions of the polymers was studied. The critical micelle concentration (CMC) was determined by a fluorescence spectroscopic analysis using the hydrophobic fluorescent dye pyrene. Results DATT-functionalized linear OEG, four-arm DAT-functionalized OEG and four-arm DATT-functionalized OEG were synthesized with degrees of functionalization of 60–95 mol%. All compounds were water soluble, and rheological measurements revealed a decrease in storage modulus G′ and loss modulus G″ compared to unfunctionalized OEG. Moreover, the CMC of linear OEG-DATT could be determined. Conclusions The syntheses of OEG functionalized with the aromatic compounds DAT and DATT was reported. The polymers showed the properties of a surfactant.

Synthesis and characterization of star-shaped oligo(ethylene glycol) with tyrosine derived moieties under variation of their molecular weight.

Desamino tyrosine (DAT) and desamino tyrosyl tyrosine (DATT) can be used to functionalize the end groups of water soluble polymers. The phenolic groups may enable physical interactions by π- π interaction and hydrogen bonds, which might lead to the formation of a hydrogel by physical crosslinking. However, using star-shaped oligo(ethylene glycols) (sOEG) with a molecular weight of 5 kDa for functionalization with DAT or DATT resulted in the formation of surfactants and not in hydrogels.As the molecular weight of the sOEG polymer chain can have an influence on forming physical cross links, DAT(T)-fuctionalization of sOEGs with higher molecular weight was investigated, the polymers were structurally characterized and for their mechanical properties were evaluated by rheological measurements.Aqueous solutions of DAT(T)-sOEGs with 10 and 20 kDa showed lower storage and loss moduli compared to unfunctionalized sOEGs indicating also the formation of surfactants. Cell-based assays showed that all sOEG solutions did not impair cell viability and were free of endotoxins, which could otherwise induce uncontrolled immune responses.Conclusively, our data suggested that the sOEG solutions have surface active properties without inducing unwanted cellular responses, which is required e.g. in pharmaceutical applications to solubilize hydophobic substances.