A Sequence-Defined ABC Dendritic Macromolecule with Amino Acid Peripheral Functionality via Iterative Chemoselective Reactions

Chemoselective reactions allow near-precision control over the polymer composition and topology to create sequence-controlled polymers with similar secondary and tertiary structures to those found in proteins. Dendrimers are recognized as well-defined macromolecules with the potential to mimic protein surface functionality due to the large number of functional groups available at its periphery with the internal structure acting as the support scaffold. Transitioning from using small-molecule dendrimers to dendritic macromolecules will not only allow retention of the high peripheral functionality but also provide an internal scaffold with a desired polymer composition within each generational layer. Here, we exemplify a systematic approach to creating a dendritic macromolecule with the placement of different polymer building blocks in precise locations within the internal structure and the placement of three different amino acid moieties clustered at the periphery. The synthesis of this ABC dendritic macromolecule was accomplished through iterative chemoselective reactions.