Related Experiment Video
Updated: May 9, 2025
13:37
Split-and-pool Synthesis and Characterization of Peptide Tertiary Amide Library
Published on: June 20, 2014
18.0K
Palindromic peptide foldamers: a strategy for structural stability and cellular uptake
Minami Fujita1,2, Takahito Ito1, Akihiko Inokuma1,2
1Division of Organic Chemistry, National Institute of Health Sciences, 3-25-26, Tonomachi, Kawasaki, Kanagawa 210-9501, Japan. demizu@nihs.go.jp.
Organic & Biomolecular Chemistry
|May 2, 2025
Summary
Researchers developed a stable peptide therapeutic using L-leucine and L-arginine. This peptide foldamer shows enhanced cellular uptake, addressing key limitations for peptide drug development.
Area of Science:
- Medicinal Chemistry
- Biotechnology
- Structural Biology
Background:
- Mid-sized peptide therapeutics offer advantages over small molecules and biologics.
- Key challenges include poor stability and limited cellular permeability, hindering clinical use.
Purpose of the Study:
- To design and characterize a novel peptide foldamer for improved therapeutic properties.
- To evaluate the structural stability and cellular uptake of the designed peptide.
Main Methods:
- Peptide design utilizing L-leucine and L-arginine residues in a palindromic sequence.
- Circular Dichroism (CD) spectroscopy to assess secondary structure and stability.
- Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (LC-MS/MS) and flow cytometry for cellular uptake analysis.
Main Results:
- The designed peptide foldamer adopted a stable alpha-helical conformation, confirmed by CD spectroscopy, even under denaturing conditions.
- Efficient intracellular delivery was observed, indicating enhanced membrane permeability due to the peptide's amphiphilic nature.
- The study demonstrates successful design of a stable and cell-permeable peptide.
Conclusions:
- The developed peptide foldamer exhibits promising structural stability and efficient cellular uptake.
- This work provides a foundation for designing advanced peptide therapeutics with enhanced functionality.
- The findings highlight the potential of amphiphilic peptide foldamers in overcoming delivery challenges for peptide drugs.
Related Concept Videos
01:25Protein Folding
7.5K
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...
7.5K
03:03Amyloid Fibrils
9.0K
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,...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
9.0K
01:13Protein Organization
135.6K
Overview
135.6K
03:00Molecular Chaperones and Protein Folding
17.6K
The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
The...
17.6K
01:39Mechanism of Filopodia Formation
2.2K
Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
2.2K
01:29Protein Folding Quality Check in the RER
3.6K
ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
3.6K