Double-stranded RNA (dsRNA) is a major impurity that can induce innate immune responses and cause adverse drug reactions. Removing dsRNA is an essential and non-trivial process in manufacturing mRNA. Current methods for dsRNA elimination use either high-performance liquid chromatography or microcrystalline cellulose, rendering the process complex, expensive, toxic, and/or time-consuming.
View Article and Find Full Text PDFWater insolubility poses a significant challenge in the clinical applications of many small molecule drugs. To improve the drug delivery efficiency, two branched amphiphilic peptides (BAPs) were designed in a computer-aided manner, for drug-loading through peptide self-assembling. The structures of the two BAPs, bis(LVFFA)-K-RGD (PepV-1) and bis(FHF)-K-RGD (PepV-2), were inspired by phospholipids, containing the RGD sequence as the hydrophilic head and two hydrophobic sequences as the hydrophobic tails.
View Article and Find Full Text PDFHighly efficient and safe non-viral vectors for nucleic acids delivery have attracted much attention due to their potential applications in gene therapy, gene editing and vaccination against infectious diseases, and various materials have been investigated and designed as delivery vectors. Herein, we designed a series of branched amphiphilic peptides (BAPs) and tested their applications as pDNA/mRNA delivery vectors. The BAP structure was inspired by the phospholipids, in which lysine oligomers were used as the "polar head", segments containing phenylalanine, histidine and leucine were used as the "hydrophobic tails", and a lysine residue was used as the branching point.
View Article and Find Full Text PDFMisfolding of TATA-box binding protein-associated factor 15 (TAF15) may cause neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS). Some mutations of prion-like domain (PrLD) have been detected in patients with sporadic ALS, suggesting the importance of TAF15-PrLD in ALS pathogenesis. Herein, combining experiments and molecular dynamics (MD) simulations, we investigated the influences of several TAF15-PrLD mutations on the amyloid fibril formation of TAF15-PrLD-extracted peptide segments, and identified an essential β-amyloid-forming segment from TAF15-PrLD.
View Article and Find Full Text PDFThis work demonstrates a self-assembling peptide strategy to form finite, molecularly defined trigonal bipyramidal-like hexamers which offer control over multivalent ligand display for enhanced tumor targeting.
View Article and Find Full Text PDFInt J Biochem Cell Biol
February 2017
Lytic and cell-penetrating peptides (CPPs) are both membrane-active peptides sharing similar physicochemical properties. Although their respective functions have been intensively investigated, the difference of intrinsic properties between these two types of peptides is rarely discussed. In this study, we designed a series of analogs of a recently discovered CPP ZXR-1 (FKIGGFIKKLWRSKLA) by varying the charge distributions both on the helical wheel projection and along the sequence.
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