TY - JOUR T1 - Dendrimer-like supramolecular assembly of proteins with a tunable size and valency through stepwise iterative growth JF - bioRxiv DO - 10.1101/2021.06.23.449676 SP - 2021.06.23.449676 AU - Jin-Ho Bae AU - Hong-Sik Kim AU - Gijeong Kim AU - Ji-Joon Song AU - Hak-Sung Kim Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/06/24/2021.06.23.449676.abstract N2 - The assembly of proteins in a programmable manner provides insight into the underlying mechanisms of protein self-assembly in nature as well as the creation of novel functional nanomaterials for practical applications. Despite many advances, however, a rational protein assembly with an easy scalability in terms of size and valency remains a challenging task. Here, we present a simple bottom-up approach to the supramolecular protein assembly with a tunable size and valency in a programmable manner. The dendrimer-like protein assembly, called a “prodrimer,” was constructed using a total of three monomeric proteins: a core and two building-block proteins. The prodrimer generations were grown by a stepwise and alternate addition of a building block using two pairs of orthogonal protein-peptide interactions, leading to a higher-generation prodrimer with a mega-dalton size and multi-valency. The valency of the prodrimers at the periphery was tunable with the generation, enabling a single-step functionalization. A second-generation prodrimer functionalized with a target-specific protein binder showed a three-order of magnitude increase in binding affinity compared to a monomeric counterpart due to the avidity. The prodrimers functionalized with a targeting moiety and a cytotoxic protein cargo exhibited a highly enhanced cellular cytotoxicity, exemplifying their utility as a protein delivery platform. The present approach can be effectively used in the creation of protein architectures with new functions for biotechnological and medical applications.Competing Interest StatementThe authors have declared no competing interest. ER -