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海天天意

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[资源] Acc. Chem. Res.10.30新鲜在线：超分子设计用于精准疗法

Programming Supramolecular Biohybrids as Precision Therapeutics
David Yuen Wah Ng,‡ Yuzhou Wu,‡ Seah Ling Kuan, and Tanja Weil*

CONSPECTUS: Chemical programming of macromolecular structures to instill a set of defined chemical properties designed to behave in a sequential and precise manner is a characteristic vision for creating next generation nanomaterials. In this context, biopolymers such as proteins and nucleic acids provide an attractive platform for the integration of complex chemical design due to their sequence specificity and geometric definition, which allows accurate translation of chemical functionalities to biological activity. Coupled with the advent of amino acid specific modification techniques, “programmable” areas of a protein chain become exclusively available for any synthetic customization. We envision that chemically reprogrammed hybrid proteins will bridge the vital link to overcome the limitations of synthetic and biological materials, providing a unique strategy for tailoring precision therapeutics.
In this Account, we present our work toward the chemical design of proteinderived hybrid polymers and their supramolecular responsiveness, while
summarizing their impact and the advancement in biomedicine. Proteins, in their native form, represent the central framework
of all biological processes and are an unrivaled class of macromolecular drugs with immense specificity. Nonetheless, the route of
administration of protein therapeutics is often vastly different from Nature’s biosynthesis. Therefore, it is imperative to chemically
reprogram these biopolymers to direct their entry and activity toward the designated target. As a consequence of the innate
structural regularity of proteins, we show that supramolecular interactions facilitated by stimulus responsive chemistry can be
intricately designed as a powerful tool to customize their functions, stability, activity profiles, and transportation capabilities.
From another perspective, a protein in its denatured, unfolded form serves as a monodispersed, biodegradable polymer scaffold
decorated with functional side chains available for grafting with molecules of interest. Additionally, we are equipped with
analytical tools to map the fingerprint of the protein chain, directly elucidating the structure at the molecular level. Contrary to
conventional polymers, these biopolymers facilitate a more systematic avenue to investigate engineered macromolecules, with
greater detail and accuracy. In this regard, we focus on denaturing serum albumin, an abundant blood protein, and exploit its
peptidic array of functionalities to program supramolecular architectures for bioimaging, drug and gene delivery. Ultimately, we
seek to assimilate the evolutionary advantage of these protein based biopolymers with the limitless versatility of synthetic
chemistry to merge the best of both worlds.

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2014-10-31 08:31:26, 716.6 K