Degradable High Molecular Weight Monodisperse Dendritic Poly(ethylene glycols)

Poly(ethylene glycols) (PEGs) are extensively explored by the pharma industry as foundations for new therapeutic products. PEGs are typically used for their conjugation to active drugs, peptides, and proteins and the likeliness to increase the half-life and enhance the therapeutic outcome. Considering the necessity of batch-to-batch consistency for clinical products, monodisperse PEGs are highly attractive but are generally limited to 5 kDa as an upper molecular weight (M_w) and with an oligomer purity of 95%. By amalgamating short, monodisperse PEGs with dendritic frameworks based on 2,2-bis(methylol)propionic acid polyesters, we showcase a robust synthetic approach to monodisperse PEGs with M_w ranging from 2 to 65 kDa. The latter is, to our knowledge, the highest M_w structure of its kind ever reported. Importantly, the dendritic multifunctional connector facilitated degradability at pH 7.4 at 37 °C, which is an important feature for the delivery of therapeutic agents.