Dataset Information

A Modular Method for the High-Yield Synthesis of Site-Specific Protein-Polymer Therapeutics.

ABSTRACT: A versatile method is described to engineer precisely defined protein/peptide-polymer therapeutics by a modular approach that consists of three steps: 1)?fusion of a protein/peptide of interest with an elastin-like polypeptide that enables facile purification and high yields; 2)?installation of a clickable group at the C?terminus of the recombinant protein/peptide with almost complete conversion by enzyme-mediated ligation; and 3)?attachment of a polymer by a click reaction with near-quantitative conversion. We demonstrate that this modular approach is applicable to various protein/peptide drugs and used it to conjugate them to structurally diverse water-soluble polymers that prolong the plasma circulation duration of these proteins. The protein/peptide-polymer conjugates exhibited significantly improved pharmacokinetics and therapeutic effects over the native protein/peptide upon administration to mice. The studies reported here provide a facile method for the synthesis of protein/peptide-polymer conjugates for therapeutic use and other applications.

SUBMITTER: Pang Y

PROVIDER: S-EPMC5320947 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A Modular Method for the High-Yield Synthesis of Site-Specific Protein-Polymer Therapeutics.

Pang Yan Y Liu Jinyao J Qi Yizhi Y Li Xinghai X Chilkoti Ashutosh A

Angewandte Chemie (International ed. in English) 20160721 35

A versatile method is described to engineer precisely defined protein/peptide-polymer therapeutics by a modular approach that consists of three steps: 1) fusion of a protein/peptide of interest with an elastin-like polypeptide that enables facile purification and high yields; 2) installation of a clickable group at the C terminus of the recombinant protein/peptide with almost complete conversion by enzyme-mediated ligation; and 3) attachment of a polymer by a click reaction with near-quantitativ ...[more]

PMID: 27439953

Similar Datasets

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

A Modular Method for the High-Yield Synthesis of Site-Specific Protein-Polymer Therapeutics.

Publications

A Modular Method for the High-Yield Synthesis of Site-Specific Protein-Polymer Therapeutics.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure