Article
Chemistry, Physical
Chad I. Drexler, Jenee D. Cyran, Lauren J. Webb
Summary: The cell-penetrating peptide NAF-1 shows promise in selectively penetrating and destroying cancer cells. Its membrane penetration and translocation are influenced by the lipid composition of the model lipid bilayer vesicles, particularly the presence of phosphatidic acid.
JOURNAL OF PHYSICAL CHEMISTRY B
(2023)
Article
Multidisciplinary Sciences
Diego Munoz-Gacitua, Fanny Guzman, Boris Weiss-Lopez
Summary: Crossing the cellular membrane is a major barrier in drug discovery, and cell-penetrating peptides are considered a promising solution. This study finds the equilibrium structure of a hydrophobic penetrating peptide and reveals a two-step mechanism for it to translocate the membrane.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Takuma Kato, Yuki Kita, Kazuki Iwanari, Akiko Asano, Makoto Oba, Masakazu Tanaka, Mitsunobu Doi
Summary: The introduction of dAAs containing both natural and unnatural amino acids can enhance the cellular uptake and membrane permeability of novel CPPs. The size of the dAA ring has a significant impact on cellular uptake, while the number of carbon atoms in the side chain ring has minimal effect.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Seungho Choe
Summary: In this study, we used the weighted ensemble method to observe the spontaneous translocation of a single Arg(9) peptide across a DOPC/DOPG(4:1) model membrane within a few tens of nanoseconds. We found that water molecules and the orientation of Arg(9) played important roles in the translocation process and showed how lipid molecules were transported with Arg(9). Additionally, we presented the free energy profiles of translocation and demonstrated that translocation of a single Arg(9) was energetically unfavorable. We expect that the weighted ensemble method can facilitate the study of interactions between cell-penetrating peptides and various model membranes in molecular dynamics simulations.
SCIENTIFIC REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Ludovic Carlier, Damien Samson, Lucie Khemtemourian, Alain Joliot, Patrick F. J. Fuchs, Olivier Lequin
Summary: By studying the behavior of EnHD in lipid bicelles, we gain insights into the molecular mechanisms of membrane translocation events in simulated membrane environments such as water and micelles. EnHD shows a global unfolding of helices in the membrane, while maintaining near-native backbone conformations. The findings have important implications for understanding the interaction mechanisms between transcription factors and membranes.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2022)
Article
Biochemistry & Molecular Biology
Binhan Hao, Wenjie Zhou, Steven M. Theg
Summary: The TMH lengths of TatA and TatB are evolutionarily tuned to 15 amino acids, with activity dropping off following any modification of this length. Even with as few as 11 residues, TatA and TatB can still insert into the membrane bilayer, albeit with a decline in membrane integrity. These findings support a model of Tat transport utilizing toroidal pores formed when the membrane bilayer reaches a critical threshold.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Microbiology
Bruna Agrillo, Alessandra Porritiello, Lorena Gratino, Marco Balestrieri, Yolande Therese Proroga, Andrea Mancusi, Loredana Cozzi, Teresa Vicenza, Principia Dardano, Bruno Miranda, Pablo V. Escriba, Marta Gogliettino, Gianna Palmieri
Summary: This study investigated the structural and functional characteristics of lysine-to-arginine substitution in antimicrobial peptides (AMPs), and reported the properties of a new RiLK1 derivative named RiLK3. The results showed that lysine-to-arginine replacement not only did not improve the antimicrobial activity of RiLK1, but completely abolished its activity against the hepatitis A virus. Therefore, the substitution of lysine with arginine has complex effects on antimicrobial efficacy and selectivity.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Piya Patra, Raja Banerjee, Jaydeb Chakrabarti
Summary: This study uses molecular dynamics simulations to investigate the interaction between HIV-1 Tat peptide and a model dipalmitoylphosphatidylcholine (DPPC) lipid bilayer in the presence of a biphosphate salt solvent. The study shows that the biphosphate salt causes the basic residues of the peptide to be repelled by the phosphate head groups of the lipid molecules, while the polar residue prefers to stay near the bilayer. This results in non-uniform thickness distribution of the bilayer structure.
Article
Biochemical Research Methods
K. G. Schaefer, A. E. Pittman, F. N. Barrera, G. M. King
Summary: Peptides that bind lipid membranes and cause leakage play important roles in cellular activities and potential therapeutic applications. The atomic force microscope (AFM) can provide precise imaging of lipid bilayer remodeling induced by membrane permeabilizing peptides to advance understanding of their mechanisms of action. High precision AFM data, coupled with robust statistical analyses, has the potential to uncover more insights into this important peptide family.
Review
Pharmacology & Pharmacy
Manon Berger, Anna Lechanteur, Brigitte Evrard, Geraldine Piel
Summary: RNA interference is a promising mechanism for gene silencing and disease treatment, but the stability of siRNA in blood is a challenge. Lipoplexes and LNPs are commonly used to deliver and protect siRNA, yet clinical translation remains difficult with only few RNAi drugs approved by the FDA. Innovative formulations incorporating pH-sensitive lipids, peptides, and polymers aim to enhance siRNA efficacy for effective antitumor effects in complex tumor environments.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Review
Biochemistry & Molecular Biology
Minglu Hao, Lei Zhang, Pu Chen
Summary: Cell-penetrating peptides (CPPs) have the ability to deliver chemical drugs, nucleic acids, and macromolecules into cells, and understanding their membrane internalization mechanisms and design strategies is of great importance. Arginine-rich peptides, with their unique cell penetration properties, have attracted significant attention. The penetration ability of arginine-rich peptides is related to the number of arginine residues, arginine optical isomers, primary sequence, secondary and ternary structures, etc. Applications of arginine-rich peptides include drug/RNA delivery systems, biosensors, and blood-brain barrier penetration, among others.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Jingxue Nai, Jinbang Zhang, Jiaxin Li, Hui Li, Yang Yang, Meiyan Yang, Yuli Wang, Wei Gong, Zhiping Li, Lin Li, Chunsheng Gao
Summary: A new treatment system was developed by combining thermosensitive liposomes with the macrophage membrane, tumor-targeting cyclic Arg-Gly-Asp peptide, a cell-penetrating peptide, and thermotherapy. This system demonstrated significant uptake and apoptosis in cancer cells, along with the strongest inhibition of Bcl-2 gene and protein. In tumor-bearing mice, the system showed excellent distribution and therapeutic efficacy, making it a promising candidate for precise tumor-targeted therapy.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Article
Biochemistry & Molecular Biology
Sung-Tae Yang, Song-Yub Shin, Sung-Heui Shin
Summary: The PXXP motif in PMAP-23 plays a crucial role in its translocation across lipid bilayers by interacting with negatively charged bacterial membranes, and wild-type PMAP-23 has stronger antimicrobial activity compared to its Pro-substituted derivatives.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Physical
Taiki Shigematsu, Kenichiro Koshiyama
Summary: Shear flow can suppress surfactant bilayer undulation and generate negative tension, which is important for the onion transition. Molecular dynamics simulations of single phospholipid bilayer under shear flow show that increasing shear rate suppresses undulation and increases negative tension, consistent with theoretical predictions. The force components of negative tension are anisotropic but the resultant tension is isotropic.
JOURNAL OF CHEMICAL PHYSICS
(2023)
Article
Pharmacology & Pharmacy
Tamara Lutzenburg, Nele Burdina, Matthias S. Scholz, Ines Neundorf
Summary: Cell-penetrating peptides (CPPs) are used to increase the intracellular accumulation of cargoes by forming stable secondary structures at the outer surface of the plasma membrane. Incorporation of hydrophobic moieties like carboranes (CBs) can alter the lipophilicity of peptides and enhance secondary structure formation, leading to potential applications in nucleic acid delivery.