Hybrid Cyclic-Linear Peptides Combine Best of Both Worlds for Drug Delivery Into Cells
Novel hybrid cyclic-linear cell-penetrating peptides with alternating charged and hydrophobic residues showed enhanced cellular uptake and molecular transport capability compared to conventional linear CPPs.
Quick Facts
What This Study Found
Hybrid cyclic-linear CPPs with alternative positively charged and hydrophobic amino acids showed enhanced cellular uptake and delivery of cell-impermeable, negatively charged molecules.
Key Numbers
18-fold uptake increase (CCRF-CEM); 11-fold (SK-OV-3); no toxicity at 10 μM; partial endocytosis independence
How They Did This
Synthesis and biological evaluation of a novel series of hybrid cyclic-linear peptides. Cellular uptake measured with various cargo molecules.
Why This Research Matters
Better CPP architectures mean more efficient drug delivery into cells. The hybrid approach addresses limitations of both pure linear (unstable) and pure cyclic (rigid) CPPs.
The Bigger Picture
CPP design is evolving from simple linear sequences to sophisticated architectures. Hybrid designs that optimize both membrane interaction and cargo binding could become standard platforms for intracellular drug delivery.
What This Study Doesn't Tell Us
In vitro uptake study. Cargo diversity limited. In vivo delivery and therapeutic applications not tested. Manufacturing complexity of hybrid peptides.
Questions This Raises
- ?Which hybrid design provides the best balance of uptake efficiency and cargo capacity?
- ?Can hybrid CPPs deliver therapeutic proteins or nucleic acids in vivo?
- ?Do hybrid architectures improve peptide stability in biological fluids?
Trust & Context
- Key Stat:
- Best of both architectures Hybrid cyclic-linear design combines cyclic stability with linear flexibility, achieving better cellular uptake than conventional CPP designs
- Evidence Grade:
- Low evidence grade: in vitro cellular uptake study with novel peptide architecture.
- Study Age:
- Published 2021.
- Original Title:
- Hybrid Cyclic-Linear Cell-Penetrating Peptides Containing Alternative Positively Charged and Hydrophobic Residues as Molecular Transporters.
- Published In:
- Molecular pharmaceutics, 18(10), 3909-3919 (2021)
- Authors:
- Khayyatnejad Shoushtari, Sorour, Zoghebi, Khalid(2), Sajid, Muhammad Imran(2), Tiwari, Rakesh Kumar, Parang, Keykavous
- Database ID:
- RPEP-05496
Evidence Hierarchy
Frequently Asked Questions
What is a hybrid cyclic-linear peptide?
It's a peptide that has part of its chain formed into a ring (cyclic) with the rest remaining a straight chain (linear). This combines the ring's structural stability with the chain's flexibility, creating better cell-penetrating properties.
Why alternate positive and hydrophobic amino acids?
Cell membranes have both charged and oily (hydrophobic) regions. Alternating positive and hydrophobic groups in the peptide optimizes interaction with both membrane components, enabling the peptide to cross more efficiently.
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Cite This Study
https://rethinkpeptides.com/research/RPEP-05496APA
Khayyatnejad Shoushtari, Sorour; Zoghebi, Khalid; Sajid, Muhammad Imran; Tiwari, Rakesh Kumar; Parang, Keykavous. (2021). Hybrid Cyclic-Linear Cell-Penetrating Peptides Containing Alternative Positively Charged and Hydrophobic Residues as Molecular Transporters.. Molecular pharmaceutics, 18(10), 3909-3919. https://doi.org/10.1021/acs.molpharmaceut.1c00594
MLA
Khayyatnejad Shoushtari, Sorour, et al. "Hybrid Cyclic-Linear Cell-Penetrating Peptides Containing Alternative Positively Charged and Hydrophobic Residues as Molecular Transporters.." Molecular pharmaceutics, 2021. https://doi.org/10.1021/acs.molpharmaceut.1c00594
RethinkPeptides
RethinkPeptides Research Database. "Hybrid Cyclic-Linear Cell-Penetrating Peptides Containing Al..." RPEP-05496. Retrieved from https://rethinkpeptides.com/research/khayyatnejad-2021-hybrid-cycliclinear-cellpenetrating-peptides
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.