Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Solid-phase aggregation of proteins under pharmaceutically relevant conditions

H R Costantino1, R Langer, A M Klibanov

  • 1Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge 02139.

Journal of Pharmaceutical Sciences
|December 1, 1994
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Protection of immobilized sulfhydryl groups against autooxidation by alterations in their microenvironment.

Applied biochemistry and biotechnology·2013
Same author

Application of immobilized hydrogenase to h2 storage in concentrated solutions of methyl viologen.

Applied biochemistry and biotechnology·2013
Same author

Reusable evanescent wave DNA biosensor for rapid, highly sensitive, and selective detection of mercury ions.

Biosensors & bioelectronics·2011
Same author

Correlation between catalytic activity and secondary structure of subtilisin dissolved in organic solvents.

Biotechnology and bioengineering·2008
Same author

Thermodynamic analysis of solvent effect on substrate specificity of lyophilized enzymes suspended in organic media.

Biotechnology and bioengineering·2008
Same author

Quantitative comparison of polyethylenimine formulations and adenoviral vectors in terms of intracellular gene delivery processes.

Gene therapy·2005

Understanding protein aggregation mechanisms is key for stable pharmaceutical formulations. This review details covalent and noncovalent aggregation pathways to improve drug stability and efficacy.

Area of Science:

  • Biochemistry
  • Pharmaceutical Sciences
  • Protein Chemistry

Background:

  • Protein pharmaceuticals are crucial therapeutics but face stability challenges.
  • Aggregation of proteins in formulations reduces therapeutic value and efficacy.
  • Understanding aggregation mechanisms is essential for developing stable protein drugs.

Purpose of the Study:

  • To review the mechanistic pathways of solid protein aggregation under relevant pharmaceutical conditions.
  • To present strategies for studying protein aggregation and aggregate formation.
  • To propose and verify rational stabilization strategies based on elucidated pathways.

Main Methods:

  • Mechanistic analysis of aggregate formation in solid proteins.
  • Investigation of both covalent and noncovalent aggregation pathways.

Related Experiment Videos

  • Review of experimental strategies for studying protein aggregation.

    • Main Results:

    • Elucidation of thiol-disulfide interchange as an aggregation pathway for proteins with disulfide bonds and free thiols.
    • Identification of beta-elimination and disulfide scrambling as aggregation mechanisms for proteins with disulfides but no free thiols.
    • Characterization of aggregation routes for proteins lacking cysteine/cystine residues, including noncovalent pathways.

    Conclusions:

    • Knowledge of aggregation mechanisms enables the development of rational stabilization strategies.
    • Verified strategies can lead to more stable and effective pharmaceutical protein formulations.
    • Mechanistic understanding is critical for advancing protein-based therapeutics.