Design, synthesis and characterization of thiol reactive dendrons for bioconjugation

Abstract

Proteins and peptides are among the key bio-molecules which have gained considerable value as therapeutic agents in recent years. Proteins and peptides not only construct the structural material of bodily tissues, but also play an important role in various regulatory functions in the organism. The apparent size of a protein or a peptide is small, thus leading to easy filtration from the kidneys that results in a short circulation time in the body. Also peptide based drugs are prone to rapid degradation by various peptide cleaving enzymes found in the body. In order to improve the therapeutic value of proteins and peptides, novel protein-polymer conjugates can be designed that can shield them from unwanted enzymatic degradation, increase the solubility, and prolong the residence time of protein or peptide-based drugs. This thesis project focused on the synthesis of well-defined dendritic structures that can be used to synthesize multiarm polymers for protein-polymer conjugation. Three generations of dendrons containing a thiol reactive functional group, at their focal point were synthesized. Novel polyester dendrons that are biocompatible and biodegradable were synthesized and characterized for their purity and elemental composition via 1H-NMR, 13C-NMR, high resolution mass spectrometry (HRMS) and FTIR spectroscopy. In addition to these, the effect of the number of generations on the rate of thiol addition reaction was investigated using UV-Vis spectroscopy.