Related Experiment Video
Updated: Feb 6, 2026
07:19
Visualizing and Analyzing Intracellular Transport of Organelles and Other Cargos in Astrocytes
Published on: August 28, 2019
8.3K
Multimeric Amphipathic α-Helical Sequences for Rapid and Efficient Intracellular Protein Transport at Nanomolar
Jae Hoon Oh1, Seung-Eun Chong1, Sohee Nam1
1Department of Chemistry Seoul National University 1 Gwanak-ro Gwanak-gu Seoul 08826 Republic of Korea.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|August 22, 2018
Summary
Multimeric cell penetrating peptides (CPPs) based on leucine and lysine show enhanced cell penetration via macropinocytosis. These novel CPPs enable efficient intracellular delivery of therapeutic molecules at low concentrations.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Cell penetrating peptides (CPPs) are crucial for intracellular delivery.
- Existing CPPs like Tat peptide require high concentrations for effective delivery.
- Optimizing CPP structure can enhance cellular uptake and reduce required concentrations.
Purpose of the Study:
- To develop multimeric leucine (L) and lysine (K)-rich α-helical peptides (LK-CPPs) with maximized cell penetration.
- To investigate the mechanism and efficiency of multimeric LK-CPPs compared to monomeric forms and Tat peptide.
- To demonstrate the potential of multimeric LK-CPPs for biomedical applications, such as gene delivery.
Main Methods:
- Design and synthesis of multimeric LK-based CPPs utilizing helix-loop-helix structures.
- Assessment of cell penetration activity in protein-fused forms at varying concentrations.
- Analysis of cellular uptake mechanisms, including macropinocytosis and the role of heparan sulfate proteoglycan (HSPG) receptors.
- Proof-of-concept delivery of peroxisome proliferator-activated receptor gamma 2 (PPAR-γ2) into preadipocytes.
Main Results:
- Multimeric LK-CPPs demonstrated significantly enhanced cell penetration compared to monomeric LK peptides and Tat peptide, requiring 100-1000 fold lower concentrations.
- Penetration efficiency increased with multimerization, up to the tetramer level.
- Rapid cell penetration occurred via macropinocytosis at low nanomolar concentrations, mediated by HSPG receptors.
- Successful delivery of PPAR-γ2 into preadipocytes induced enhanced adipogenic gene expression at nanomolar concentrations.
Conclusions:
- Multimerization of LK-rich α-helical peptides effectively enhances cell penetration activity.
- Multimeric LK-CPPs represent a potent platform for efficient intracellular delivery of biomacromolecules at low, therapeutically relevant concentrations.
- This technology holds promise for controlling cellular reactions and advancing biomedical applications requiring targeted intracellular delivery.
Keywords:
adipocyte differentiationcell penetrating peptidesintracellular protein transportmultimeric amphipathic α‐helical peptidesnanomolar concentrationsMore Related Videos
Related Concept Videos
02:15Protein and Protein Structure
88.2K
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...
A protein's shape is critical to its function. For example, an enzyme...
88.2K
01:16Introduction to Membrane Proteins
81.3K
The cell membrane, or plasma membrane, is an ever-changing landscape. It is described as a fluid mosaic where various macromolecules are embedded in the phospholipid bilayer. Among the macromolecules are proteins. The protein content varies across cell types. For example, mitochondrial inner membranes contain ~76% protein content, while myelin contains ~18% protein content. Individual cells contain many types of membrane proteins—red blood cells contain over 50—and different cell...
81.3K
02:21Globular and Fibrous Proteins
47.1K
Many proteins can be classified into two distinct subtypes - globular or fibrous. These two types differ in their shapes and solubilities.
Globular proteins are also known as spheroproteins and typically are approximately round in shape. They contain a mix of amino acid types and contain differing sequences in their primary structures. Globular proteins have many different functions, such as enzymes, cellular messengers, and molecular transporters. These roles often require the proteins to be...
Globular proteins are also known as spheroproteins and typically are approximately round in shape. They contain a mix of amino acid types and contain differing sequences in their primary structures. Globular proteins have many different functions, such as enzymes, cellular messengers, and molecular transporters. These roles often require the proteins to be...
47.1K
02:47Protein Families
17.0K
Protein families are groups of homologous proteins; that is, they have similarities in amino acid sequences and three-dimensional structures. Protein families usually occur because of gene duplication, where an additional copy of a gene is inserted into the genome of an organism. Mutations that change the amino acids but still allow the protein to be properly synthesized, will lead to new protein family members. If these new proteins contain similar amino acids in key...
17.0K
01:47Primary Active Transport
199.4K
In contrast to passive transport, active transport involves a substance being moved through membranes in a direction against its concentration or electrochemical gradient. There are two types of active transport: primary active transport and secondary active transport. Primary active transport utilizes chemical energy from ATP to drive protein pumps that are embedded in the cell membrane. With energy from ATP, the pumps transport ions against their electrochemical gradients—a direction...
199.4K
02:02Cis-regulatory Sequences
11.9K
Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
11.9K