Dendrimer-Like Supramolecular Assembly of Proteins with a Tunable Size and Valency Through Stepwise Iterative Growth

通过逐步迭代生长实现具有可调尺寸和价态的树枝状蛋白质超分子组装

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Abstract

The assembly of proteins in a programmable manner provides insight into 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 challenge. Here, a simple bottom-up approach to the supramolecular protein assembly with a tunable size and valency in a programmable manner is presented. The dendrimer-like protein assembly, simply called a "protein dendrimer," is constructed through a stepwise and alternate addition of a building block protein. Starting from zeroth-generation protein dendrimer (pG(0) ) of 27 kDa, the protein dendrimer is sequentially grown to pG(1) , pG(2) , pG(3) , to pG(4) with a molecular mass of 94, 216, 483, and 959 kDa, respectively. The valency of the protein dendrimers at the periphery increases by a factor of two after each generation, allowing a tunable valency and easy functionalization. The protein dendrimers functionalizes with a targeting moiety and a cytotoxic protein cargo shows a typical feature of multi-valency in the avidity and 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.

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