Related Experiment Video
Updated: May 14, 2026
11:09
Constructing Thioether/Vinyl Sulfide-tethered Helical Peptides Via Photo-induced Thiol-ene/yne Hydrothiolation
Published on: August 1, 2018
α-Helix mimicry with α/β-peptides
Lisa M Johnson1, Samuel H Gellman
1Department of Chemistry, University of Wisconsin, Madison, Wisconsin, USA.
Methods in Enzymology
|February 21, 2013
Summary
Researchers created novel alpha/beta-peptides with unnatural backbones that mimic natural alpha-helices. These peptides show resistance to degradation and can block harmful protein interactions or activate cellular receptors.
Area of Science:
- Biochemistry
- Structural Biology
- Medicinal Chemistry
Background:
- Natural alpha-helices are crucial in protein-protein interactions.
- Developing stable peptide mimics is challenging due to proteolytic degradation.
Purpose of the Study:
- To design and synthesize peptidic oligomers with unnatural backbones that adopt alpha-helical conformations.
- To investigate the proteolytic stability and functional mimicry of these novel alpha/beta-peptides.
Main Methods:
- Synthesis of alpha/beta-peptides incorporating both alpha- and beta-amino acid residues.
- Conformational analysis to assess alpha-helix mimicry.
- Proteolytic degradation assays.
- Biochemical assays to evaluate protein-protein interaction modulation.
Main Results:
- Developed a general strategy for creating alpha/beta-peptides with alpha-helical structures.
- Achieved substantial resistance to proteolytic degradation with 25-30% beta-residue content.
- Demonstrated mimicry of natural alpha-helical protein domains.
- Successfully designed ligands for antiapoptotic Bcl-2 proteins and inhibitors of HIV infection.
Conclusions:
- Alpha/beta-peptides represent a promising class of unnatural oligomers for mimicking alpha-helical functions.
- These peptides can serve as antagonists or agonists in therapeutic applications.
- Potential for developing new drugs targeting protein-protein interactions and infectious diseases.
Related Concept Videos
01:25Protein Folding
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...
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
01:22Protein Folding
Overview
03:03Amyloid Fibrils
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, normally used to...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
01:13Protein Organization
Overview
01:24Protein Organization
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.
The primary structure of a protein is its amino acid sequence.
02:15Protein and Protein Structure
Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.
A protein's shape is critical to its function. For example, an enzyme can...
A protein's shape is critical to its function. For example, an enzyme can...