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 Concept Videos

Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

6.7K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
6.7K
Protein Folding01:25

Protein Folding

7.7K
Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
7.7K
Protein Organization01:24

Protein Organization

6.2K
Proteins are polymers of amino acid residues. They are versatile and responsible for different cellular functions, including DNA replication, molecular transport, catalysis, and structural support. Proteins have a hierarchical structure comprising at least three levels of organization: primary, secondary, and tertiary structure. Some large proteins have a quaternary structure where individual protein subunits are linked together.
The primary structure of a protein is its amino acid sequence....
6.2K
Protein Denaturation01:28

Protein Denaturation

3.7K
The function of proteins depends on their native three-dimensional structure, which is dictated by the amino acid sequence of the specific protein. Folding of the polypeptide chain takes place under specific conditions that energetically favor the folded conformation. In contrast, protein denaturation occurs spontaneously under unfavorable conditions that disrupt the integrity of the folded conformation. Thus, the chemical and physical environment of a protein, such as significant changes in pH...
3.7K
Protein Complex Assembly02:41

Protein Complex Assembly

10.5K
Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types.  Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
10.5K
Amyloid Fibrils03:03

Amyloid Fibrils

9.2K
Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining,...
9.2K

You might also read

Related Articles

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

Sort by
Same author

Pulsatile Release of Human Gonadotropin Releasing Hormone Using a Photoactivated Depot Containing an Unusual Light Cleaved Functionality.

Molecular pharmaceutics·2025
Same author

The Photoactivated Depot (PAD): Light Triggered Control of Therapeutic Protein Solubility and Release.

Accounts of chemical research·2025
Same author

Selective Dissolution of Calcium Pyrophosphate Dihydrate Crystals Using a Pyrophosphate Specific Receptor.

Chembiochem : a European journal of chemical biology·2024
Same author

A Green Light-Activated Insulin Depot with Ultrafast In Vivo Efficiency in the Subcutaneous Space.

ACS biomaterials science & engineering·2024
Same author

In vivo variable and multi-day response from an insulin-releasing photoactivated depot.

Bioorganic & medicinal chemistry letters·2023
Same author

A Light Activated Glucagon Trimer with Resistance to Fibrillation.

ACS biomaterials science & engineering·2021
Same journal

Apolipoprotein A-I as a Molecular Target of the Immunomodulatory Peptide Jusvinza: Mechanistic Insights From Affinity and In Silico Studies.

Journal of peptide science : an official publication of the European Peptide Society·2026
Same journal

Integrative Identification of Anti-Photoaging Peptides From Stress-Tolerant Microorganisms via Machine Learning and KEAP1-NRF2 Docking.

Journal of peptide science : an official publication of the European Peptide Society·2026
Same journal

Cementum Attachment Protein-Derived Peptides Modulate Brushite and Calcium Oxalate Crystallization In Vitro.

Journal of peptide science : an official publication of the European Peptide Society·2026
Same journal

Nanostructure and Collagen-Stimulating Activity of Cationic Pentapeptide Lipopeptides.

Journal of peptide science : an official publication of the European Peptide Society·2026
Same journal

Reductive Methylation: An Alternative to Lysine → Arginine Mutagenesis.

Journal of peptide science : an official publication of the European Peptide Society·2026
Same journal

Radiolabeled Angiopep-2 Peptide Vector as a Preclinical Platform for Blood-Brain Barrier Targeting: Synthesis, Radiolabeling, and Preliminary In Vivo Biodistribution in Mice.

Journal of peptide science : an official publication of the European Peptide Society·2026
See all related articles

Related Experiment Video

Updated: May 24, 2025

Paramagnetic Relaxation Enhancement for Detecting and Characterizing Self-Associations of Intrinsically Disordered Proteins
07:24

Paramagnetic Relaxation Enhancement for Detecting and Characterizing Self-Associations of Intrinsically Disordered Proteins

Published on: September 23, 2021

1.7K

Preventing Protein Self-Association Through Strategic Covalent Modification.

Swetha Chintala1, Simon H Friedman1

  • 1Division of Pharmacology and Pharmaceutical Sciences, University of Missouri-Kansas City School of Pharmacy, Kansas City, Missouri, USA.

Journal of Peptide Science : an Official Publication of the European Peptide Society
|March 6, 2025
PubMed
Summary
This summary is machine-generated.

Researchers developed a method to prevent therapeutic protein aggregation by modifying glucagon peptides. This approach enhances protein stability and reduces fibril formation, improving drug efficacy and safety.

Keywords:
fibril formationglucagonprotein aggregationprotein modification

More Related Videos

Author Spotlight: In Silico Creation and Impact of Carbonylated Amino Acids on Protein Structure and Function
05:57

Author Spotlight: In Silico Creation and Impact of Carbonylated Amino Acids on Protein Structure and Function

Published on: April 26, 2024

308
Synthesis of Information-bearing Peptoids and their Sequence-directed Dynamic Covalent Self-assembly
09:34

Synthesis of Information-bearing Peptoids and their Sequence-directed Dynamic Covalent Self-assembly

Published on: February 6, 2020

7.1K

Related Experiment Videos

Last Updated: May 24, 2025

Paramagnetic Relaxation Enhancement for Detecting and Characterizing Self-Associations of Intrinsically Disordered Proteins
07:24

Paramagnetic Relaxation Enhancement for Detecting and Characterizing Self-Associations of Intrinsically Disordered Proteins

Published on: September 23, 2021

1.7K
Author Spotlight: In Silico Creation and Impact of Carbonylated Amino Acids on Protein Structure and Function
05:57

Author Spotlight: In Silico Creation and Impact of Carbonylated Amino Acids on Protein Structure and Function

Published on: April 26, 2024

308
Synthesis of Information-bearing Peptoids and their Sequence-directed Dynamic Covalent Self-assembly
09:34

Synthesis of Information-bearing Peptoids and their Sequence-directed Dynamic Covalent Self-assembly

Published on: February 6, 2020

7.1K

Area of Science:

  • Biochemistry
  • Pharmaceutical Science
  • Protein Engineering

Background:

  • Protein self-interaction causes aggregation, leading to reduced activity and increased immunogenicity in protein pharmaceuticals.
  • Therapeutic peptides like glucagon are prone to fibril formation due to self-association, limiting their clinical application.

Purpose of the Study:

  • To develop and evaluate a novel strategy for blocking quaternary interactions that drive protein self-association.
  • To improve the stability and fibrillation resistance of glucagon, a therapeutic peptide.

Main Methods:

  • Synthesized a regio-pure common feedstock for glucagon modification.
  • Modified glucagon with various blocking peptides (anionic, cationic, polar, nonpolar).
  • Assessed fibrillation resistance using three complementary biophysical techniques.

Main Results:

  • Identified two modified glucagon variants with significantly enhanced stability against fibril formation compared to unmodified glucagon.
  • Confirmed stabilization through multiple biophysical assays.
  • Observed that successful modifications introduced excess net charge, suggesting electrostatic repulsion as the mechanism for fibrillation resistance.

Conclusions:

  • The developed approach effectively antagonizes self-association and enhances the stability of therapeutic proteins.
  • Modification strategies, particularly those increasing net charge, can mitigate glucagon fibrillation.
  • This method holds potential for application to other therapeutic proteins susceptible to self-association issues.