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An organometallic swap strategy for bottlebrush polymer-protein conjugate synthesis.

ABSTRACT: Polymer-protein bioconjugation offers a powerful strategy to alter the physical properties of proteins, and various synthetic polymer compositions and architectures have been investigated for this purpose. Nevertheless, conjugation of molecular bottlebrush polymers (BPs) to proteins remains an unsolved challenge due to the large size of BPs and a general lack of methods to transform the chain ends of BPs into functional groups suitable for bioconjugation. Here, we present a strategy to address this challenge in the context of BPs prepared by "graft-through" ring-opening metathesis polymerization (ROMP), one of the most powerful methods for BP synthesis. Quenching ROMP of PEGylated norbornene macromonomers with an activated enyne terminator facilitates the transformation of the BP Ru alkylidene chain ends into Pd oxidative addition complexes (OACs) for facile bioconjugation. This strategy is shown to be effective for the synthesis of two BP-protein conjugates (albumin and ERG), setting the stage for a new class of BP-protein conjugates for future therapeutic and imaging applications.

SUBMITTER: Liu B

PROVIDER: S-EPMC11008127 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature

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An organometallic swap strategy for bottlebrush polymer-protein conjugate synthesis.

Liu Bin B Rodriguez Jacob J J Kilgallon Landon L Wang Wencong W Wang Yuyan Y Wang Aiden A Dai Yutong Y Nguyen Hung V-T HV Pentelute Bradley L BL Johnson Jeremiah A JA

Chemical communications (Cambridge, England) 20240411 31

Polymer-protein bioconjugation offers a powerful strategy to alter the physical properties of proteins, and various synthetic polymer compositions and architectures have been investigated for this purpose. Nevertheless, conjugation of molecular bottlebrush polymers (BPs) to proteins remains an unsolved challenge due to the large size of BPs and a general lack of methods to transform the chain ends of BPs into functional groups suitable for bioconjugation. Here, we present a strategy to address t ...[more]

PMID: 38529790

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Project description:Protein therapeutic formulations are being widely explored as multifunctional nanotherapeutics. Challenges in ensuring susceptibility and efficacy of nanoformulation still prevail owing to various interactions with biological fluids before reaching the target site. Smart polymers with the capability of masking drugs, ease of chemical modification, and multi-stimuli responsiveness can assist controlled delivery. An active moiety like therapeutic protein has started to be known as an important biological formulation with a diverse medicinal prospect. The delivery of proteins and peptides with high target specificity has however been tedious, due to their tendency to aggregate formation in different environmental conditions. Proteins due to high chemical reactivity and poor bioavailability are being researched widely in the field of nanomedicine. Clinically, multiple nano-based formulations have been explored for delivering protein with different carrier systems. A biocompatible and non-toxic polymer-based delivery system serves to tailor the polymer or drug better. Polymers not only aid delivery to the target site but are also responsible for proper stearic orientation of proteins thus protecting them from internal hindrances. Polymers have been shown to conjugate with proteins through covalent linkage rendering stability and enhancing therapeutic efficacy prominently when dealing with the systemic route. Here, we present the recent developments in polymer-protein/drug-linked systems. We aim to address questions by assessing the properties of the conjugate system and optimized delivery approaches. Since thorough characterization is the key aspect for technology to enter into the market, correlating laboratory research with commercially available formulations will also be presented in this review. By examining characteristics including morphology, surface properties, and functionalization, we will expand different hybrid applications from a biomaterial stance applied in in vivo complex biological conditions. Further, we explore understanding related to design criteria and strategies for polymer-protein smart nanomedicines with their potential prophylactic theranostic applications. Overall, we intend to highlight protein-drug delivery through multifunctional smart polymers.

Dataset Information

An organometallic swap strategy for bottlebrush polymer-protein conjugate synthesis.

Publications

An organometallic swap strategy for bottlebrush polymer-protein conjugate synthesis.

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