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Related Concept Videos

Conjugated Proteins02:50

Conjugated Proteins

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Simple proteins and protein complexes contain only amino acids. In contrast, many other proteins, called conjugated proteins, covalently bond with non-protein moieties.
Nucleoproteins are protein complexes that contain nucleic acids, categorized as deoxyribonucleoproteins (DNPs) or ribonucleoproteins (RNPs) respectively. The nucleosome is a typical example of a DNP where nuclear DNA is associated with histone proteins. The major antigen for the Covid-19 virus SARS-CoV is an RNP that is critical...
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Phase II Conjugation Reactions: Overview01:14

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Conjugation, a key component of phase II biotransformation reactions, is a vital process in drug detoxification. It involves transferring endogenous substances like glucuronic acid, sulfate, and glycine to drugs or their metabolites formed in phase I reactions. These conjugation reactions, often catalyzed by specific enzymes, transform potentially harmful metabolites into inactive, water-soluble forms easily excreted in urine or bile. By enhancing polarity and eliminating pharmacological...
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Drug Metabolism: Phase II Reactions01:14

Drug Metabolism: Phase II Reactions

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Phase II reactions are essential for the detoxification and elimination of drugs from the body. These reactions involve the conjugation of parent drugs or their phase I metabolites with endogenous molecules, resulting in more hydrophilic drug conjugates. The primary conjugation reactions in this phase are sulfation and glucuronidation. Both sulfation and glucuronidation typically produce biologically inactive metabolites. However, in some cases involving prodrugs, active metabolites may be...
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Tagging and Fusion Proteins01:24

Tagging and Fusion Proteins

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Proteins are involved in several cellular processes and biochemical reactions. Analyzing a specific protein of interest requires it to be isolated from the other proteins in the cell. This is achieved by overexpressing the specific gene in a suitable host to produce large quantities of the target protein. A tag or label is recombined with the gene to produce a fusion protein containing the target protein and the tag. The tags on these fusion proteins can then be used for easy detection and...
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Site-Targeted Drug Delivery Systems: Polymeric Carriers01:24

Site-Targeted Drug Delivery Systems: Polymeric Carriers

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Polymeric carriers enhance targeted drug delivery by increasing efficacy while minimizing off-target effects. These carriers comprise a biodegradable polymeric backbone integrated with functional elements that enable targeting, improve physicochemical properties, and regulate drug release.Targeting MechanismsThe targeting ability of polymeric carriers is mediated by a homing device, which is a molecular recognition component designed to selectively bind to specific tissues or cells. Monoclonal...
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Synthesis of Protein Bioconjugates via Cysteine-maleimide Chemistry
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Synthesis of Protein Bioconjugates via Cysteine-maleimide Chemistry

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Reversible Bioconjugation: Biodegradable Poly(phosphate)-Protein Conjugates.

Tobias Steinbach1,2, Greta Becker1,2, Alina Spiegel1

  • 1Max-Planck-Institut für Polymerforschung, Ackermannweg 10, 55128, Mainz, Germany.

Macromolecular Bioscience
|December 13, 2016
PubMed
Summary
This summary is machine-generated.

Researchers developed a biodegradable poly(phosphate) (PEEP) as a new alternative to poly(ethylene glycol) (PEG) for protein drug delivery. PEEP conjugates are the first polyphosphate-based system to degrade, offering potential for next-generation therapeutics.

Keywords:
PEGylationbiodegradable polymerpoly(phosphoester)sprotein-polymer conjugates

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OaAEP1-Mediated Enzymatic Synthesis and Immobilization of Polymerized Protein for Single-Molecule Force Spectroscopy
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Synthesis and Bioconjugation of Thiol-Reactive Reagents for the Creation of Site-Selectively Modified Immunoconjugates
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OaAEP1-Mediated Enzymatic Synthesis and Immobilization of Polymerized Protein for Single-Molecule Force Spectroscopy
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Area of Science:

  • Biomaterials Science
  • Polymer Chemistry
  • Drug Delivery Systems

Background:

  • Protein-polymer conjugates enhance therapeutic protein pharmacokinetics.
  • Current poly(ethylene glycol) (PEG) conjugates face limitations due to non-biodegradability and immunogenicity.
  • Development of biodegradable alternatives to PEG is crucial for advanced drug delivery.

Purpose of the Study:

  • To synthesize and characterize a novel biodegradable poly(phosphate) (PEEP) as a PEG alternative.
  • To create and evaluate PEEP-protein conjugates for therapeutic applications.
  • To demonstrate the degradability and functionality of PEEP-based drug delivery systems.

Main Methods:

  • Organo-catalyzed anionic ring-opening polymerization was used to synthesize PEEP with controlled molecular weights and low dispersity (< 1.3).
  • PEEP polymers were functionalized with succinimidyl carbonate groups.
  • Functionalized PEEP was conjugated to model proteins, and the resulting conjugates were tested for in vitro activity and degradability.

Main Results:

  • Biodegradable poly(ethyl ethylene phosphate) (PEEP) was successfully synthesized with molecular weights ranging from 2000 to 33,200 g mol⁻¹.
  • The synthesized PEEP-protein conjugates demonstrated degradation upon exposure to phosphodiesterase.
  • Residual in vitro activity of PEEP conjugates was dependent on the degree of protein modification, similar to PEGylated proteins.

Conclusions:

  • PEEP represents a novel, biodegradable polyphosphate-based alternative to PEG for protein conjugation.
  • These PEEP-protein conjugates are the first polyphosphate-based system shown to degrade, offering a significant advantage over non-biodegradable PEG.
  • PEEP exhibits desirable properties for next-generation, fully degradable drug delivery systems.