Cell-penetrating peptides (CPPs) provide a promising approach for enhancing intracellular delivery of therapeutic biomacromolecules by increasing transport through membrane barriers. Here, proteolytically stable cell-penetrating peptidomimetics with α-peptide/β-peptoid backbone were studied to evaluate the effect of α-chirality in the β-peptoid residues and the presence of guanidinium groups in the α-amino acid ...

Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is increasingly recognized as a central regulator of multiple signaling pathways in inflammation and cancer, and the ability to use chemical biological tools to investigate its biological effects is very attractive. A peptide comprising a TAT-conjugated Nrf2 sequence is shown to activate Nrf2 and ...

The use of nanoparticles in medicine (nanomedicine) has recently become an intensely studied field. Nanoparticles carrying drugs and imaging agents have already reached the clinic, but they are essentially passive delivery vehicles, not what are referred to as "smart" nanoparticles. An important function to add to make nanoparticles smarter is ...

Internalisation of nanoparticles conjugated with cell penetrating peptides is a promising approach to various drug delivery applications. Cell penetrating peptides such as transactivating transcriptional activator (TAT) peptides derived from HIV-1 proteins are effective intracellular delivery vectors for a wide range of nanoparticles and pharmaceutical agents thanks to their amicable ability ...

Aniline-catalyzed oxime chemistry was employed to conjugate a γ-amino-proline-derived cell penetrating peptide to superparamagnetic iron oxide nanoparticles (SPIONs). Internalization of the novel nanoconjugate into HeLa cells was found to be remarkably higher compared to the analogous TAT-SPION conjugate.

Cell-penetrating peptides (CPPs) have proven utility for the highly efficient intracellular delivery of bioactive cargoes that include peptides, proteins, and oligonucleotides. The many strategies developed to utilize CPPs solely as pharmacokinetic modifiers necessarily requires them to be relatively inert. Moreover, it is feasible to combine one or multiple CPPs with ...

The (R-X-R) motif-containing arginine-rich peptides are among the most effective cell-penetrating peptides. The replacement of amide linkages in the (R-X-R) motif by carbamate linkages as in (r-ahx-r)(4) or (r-ahx-r-r-apr-r)(2) increases the efficacy of such oligomers several-fold. Internalization of these oligomers in mammalian cell lines occurs by an energy-independent process. These ...

Cell penetrating peptides hold considerable potential for academic and pharmaceutical remits with an interest in delivering macromolecules to the insides of cells. Hundreds of sequences now fall within the cell penetrating peptide classification and the HIV-Tat peptide, penetratin, transportan, and octaarginine represent extensively studied variants. The process by which membrane ...

Arginine-rich cell-penetrating peptides (CPPs), including oligoarginine peptides, have been widely used as a tool for intracellular delivery of various molecules with low membrane permeability. We previously reported the enhanced cytosolic entry of arginine-rich CPPs by the attachment of a short peptide segment, the penetration accelerating sequence (Pas). In this study, ...

Anionic copolymer systems containing sulfated monomers have great potential for delivery of cationic therapeutics, but N-isopropylacrylamide (NIPAm) 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) copolymer nanoparticles have seen limited characterization to date with regard to physical properties relevant to loading and release of therapeutics. Characterization of polymeric nanoparticles incorporating AMPS showed an increased size ...

To deliver siRNA specifically to cardiomyocytes with high transfection efficiency, primary cardiomyocyte-targeting (PCM) and/or cell-penetrating (Tat) peptides were incorporated into the siRNA. With the addition of plasmid DNA, these peptide conjugated siRNAs were able to form compact and stable nanosized polyplex particles with bioreducible poly(CBA-DAH). The peptide-modified siRNA polyplexes enhanced ...

Skin is an important site for local or systemic application of drugs. However, majority of drugs have poor permeability through the skin's topmost layer, stratum corneum (SC). The aim of this study was to identify safe and smaller peptides that could enhance the skin penetration of drug molecules. By screening ...

Human immunodeficiency virus type 1 (HIV-1) transactivator of transcription (Tat) protein possesses a unique membrane-transduction property. Interestingly, Tat transduction could be dramatically increased 1000-fold based on LTR-transactivation assay when complexed with cationic liposomes (lipo-Tat), compared with Tat alone. Therefore, underlining mechanisms were explored further. Microscopy and flow cytometry showed that ...

With more than ten new FDA approvals since 2001, peptides are emerging as an important therapeutic alternative to small molecules. However, unlike small molecules, peptides on the market today are limited to extracellular targets. By contrast, cell-penetrating peptides (CPPs) can target intracellular proteins and also carry other cargoes (e.g. other ...

Maurocalcine is the first demonstrated example of an animal toxin peptide with efficient cell penetration properties. While it is a highly competitive cell penetrating peptide (CPP), its relatively large size of 33 amino acids and the presence of three internal disulfide bridges may hamper its development for in vitro and ...

Cell-penetrating peptides including the trans-activating transcriptional activator (Tat) from HIV-1 have been used as carriers for intracellular delivery of a myriad of cargoes including drugs, molecular probes, DNAs and nanoparticles. Utilizing fluorescence flow cytometry and confocal fluorescence microscopy, we demonstrate that a γ-AApeptide mimetic of Tat (48-57) can cross the ...

Cellular uptake of vector peptides used for internalization of hydrophilic molecules into cells is known to follow two different pathways: direct translocation of the plasma membrane and internalization by endocytosis followed by release into the cytosol. These pathways differ in their energy dependence. The first does not need metabolic energy ...

The three-dimensional structure of the ribosomal large subunit (LSU) reveals a single morphological element, although the 23S rRNA is contained in six secondary structure domains. Based upon maps of inter- and intra-domain interactions and proposed evolutionary pathways of development, we hypothesize that Domain III is a truly independent structural domain ...

Endocytosis has been implicated in the cellular uptake of arginine-rich, cell-penetrating peptides (CPPs). However, accumulating evidence suggests that certain conditions allow the direct, non-endocytic penetration of arginine-rich peptides through the plasma membrane. We previously showed that Alexa Fluor 488-labeled dodeca-arginine (R12-Alexa488) directly enters cells at specific sites on the plasma ...

BACKGROUND: Melittin is a commonly used cell penetrating peptide (CPP) for improving branched polyethylenimine (BPEI)- mediated gene transfection. However, its application is limited owing to the cytotoxicity generated by the lytic activity at neutral pH. Here, we report two truncated peptides from melittin and florae with improved transfection efficiency. METHODS: ...

This communication presents a symmetric fluorescent peptide (K(d) = 17.4 nM) for hypersensitively detecting Ag(+) in 100% aqueous solution by turn-on response. The peptide penetrated live HeLa cells and detected intracellular Ag(+) by turn-on response.

Intracellular delivery of proteins offers an alternative to genetic modification or siRNA transfection for functional studies of proteins in live cells, especially for studies in cancer cells for therapeutics development. However, lack of efficient and biocompatible delivery system has limited the use of protein for in vitro cancer research. In ...

We investigated the molecular interactions of a cell penetrating peptide (CPP) Pep-1 with model cell membranes using sum frequency generation (SFG) vibrational spectroscopy, supplemented by attenuated total reflectance - Fourier transform infrared spectroscopy (ATR-FTIR). Hydrogenated and deuterated 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol (DPPG and dDPPG) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (POPG), were used in the experiments to ...

Buforin IIb-a synthetic analog of buforin II that contains a proline hinge between the two α-helices and a model α-helical sequence at the C-terminus (3× RLLR)-is a potent cell-penetrating antimicrobial peptide. To develop novel antimicrobial peptides with enhanced activities and specificity/therapeutic index, we designed several analogs (Buf III analogs) by ...

Platinum-based drugs play a crucial role in the fight against cancer. Oxaliplatin, which is used in the treatment of colorectal carcinoma, was the last platinum-based agent to be approved worldwide. However, the efficiency of the therapy is limited for example by a low accumulation of the drug in cancer cells. ...

Cell-penetrating peptides have the ability to stimulate uptake of macromolecular cargo in mammalian cells in a non-toxic manner and therefore hold promise as efficient and well tolerated gene delivery vectors. Non-covalent peptide-DNA complexes ("peptiplexes") enter cells via endocytosis, but poor peptiplex stability and endosomal entrapment are considered as main barriers ...

Compounds which inhibit the HIV-1 replication cycle have been found amongst fragment peptides derived from an HIV-1 matrix (MA) protein. Overlapping peptide libraries covering the whole sequence of MA were designed and constructed with the addition of an octa-arginyl group to increase their cell membrane permeability. Imaging experiments with fluorescent-labeled ...

Cell-penetrating peptides (CPP), which are short peptides that are capable of crossing the plasma membrane of a living cell, are under development as delivery vehicles for therapeutic agents that cannot themselves enter the cell. One well-studied CPP is the 10-amino acid peptide derived from the human immunodeficiency virus type 1 ...

Delivering drug molecules into the cell is one of the major challenges in the process of drug development. In past, cell penetrating peptides have been successfully used for delivering a wide variety of therapeutic molecules into various types of cells for the treatment of multiple diseases. These peptides have unique ...

Cell-targeting peptides which improve tissue-specific delivery of antisense oligonucleotides (AONs) are a new exciting "next-generation" potential AON therapy. New peptides are regularly developed which increase targeting and cell penetration for the AON treatment of mRNA misregulated diseases. Optimization of these peptide conjugate AONs requires systematic treatment and methods of analysis. ...

The increasing knowledge on the genetic basis of disease provides a platform for the development of promising gene-targeted therapies that can be applied to numerous pathological conditions, including cancer. Such genetic-based approaches involve the use of nucleic acids as therapeutic agents, either for the insertion or for the repair and ...

We have explored the merits of a novel delivery strategy for the antisense oligomers based on cell penetrating peptide (CPP) conjugated to a carrier PNA with sequence complementary to part of the antisense oligomer. The effect of these carrier CPP-PNAs was evaluated by using antisense PNA targeting splicing correction of ...

A combined simulation and experimental study was performed to investigate how methanol affects the structure of a model peptide BBA5. BBA5 forms a stable β-hairpin-α-helix structure in aqueous solutions. Molecular dynamics simulations were performed in water and methanol/water solutions using all-atom explicit models. NMR experiments were used to test the ...

MHC-epitope binding plays a key role in the cellular immune response. Accurate prediction of MHC-epitope binding affinity can greatly expedite epitope screening by reducing costs and experimental effort. In this paper, 13 T descriptors， which derived from 544 physicochemical properties of the natural amino acids, were used to characterize 4 ...

We investigate the role of dynamics on adsorption of peptides to gold surfaces using all-atom molecular dynamics simulations in explicit solvent. We choose six homopolypeptides [Ala(10), Ser(10), Thr(10), Arg(10), Lys(10), and Gln(10)], for which experimental surface coverages are not correlated with amino acid level affinities for gold, with the idea ...

Selected hydrophilic interaction chromatography (HILIC) columns packed with bare silica, bridge-ethyl hybrid silica, or an amide sorbent chemistry were utilized for an investigation of chromatographic behavior and separation selectivity of tryptic peptides. Retention model was proposed allowing for retention prediction of peptides with correlation coefficient R(2)∼0.92-0.97 for various columns. The ...

In this research, the adsorption of two herbicides, alachlor (ALA) and terbuthylazine (TBA), on granular activated carbon (GAC) in the presence of well-characterized peptide fraction of cellular organic matter (COM) produced by cyanobacterium Microcystis aeruginosa was studied. Two commercially available GACs were characterized using nitrogen gas adsorption and surface charge ...

The influence of the pore size of a chromatographic reversed phase material on the adsorption equilibria and diffusion of two industrially relevant peptides (i.e. a small synthetic peptide and insulin) has been studied using seven different reversed phase HPLC materials having pore sizes ranging from 90Å to 300Å. The stationary ...

The single crystal X-ray diffraction studies of a new tripeptide motif Boc-Tyr-Aib-Xaa-OMe (Xaa = Leu/Ile/Ala) reveal that the peptides adopt β-turn conformations which self-assemble to form a supramolecular double helical structure using various non-covalent interactions in the solid state and the peptides exhibit a type-III N(2) sorption isotherm.

The kinetics of adsorption and desorption of two highly asymmetrical model peptides were studied at methyl- and carboxylic acid-terminated alkylthiolate self-assembled monolayer (SAM) surfaces on gold. The model peptides were leucine-lysine (LK), α-helical (LKα14), and β-strand (LKβ15) peptides that have a well-defined secondary structure with the leucines localized on one ...

We report the effects of peptide adsorption to cross-linked polymers (adsorbents) by its conformational changes. Two adsorbents, APhe and ALeu, were prepared and expected to show high affinity to the oligopeptide VW-8 (NH(2)-Val-Val-Arg-Gly-Cys-Thr-Trp-Trp-COOH) according to our previous studies. These absorbents bared the residues of phenylalanine and leucine, respectively, and carried ...

Surface plasmon resonance (SPR) spectroscopy is a useful technique for thermodynamically characterizing peptide-surface interactions; however, its usefulness is limited to the types of surfaces that can readily be formed as thin layers on the nanometer scale on metallic biosensor substrates. Atomic force microscopy (AFM), on the other hand, can be ...

Mimochrome VI (MC-VI) is a synthetic heme peptide containing a helix-heme-helix sandwich motif designed to reproduce the catalytic activity of heme oxidases. The thermodynamics of Fe(III) to Fe(II) reduction and the kinetics of the electron-transfer process for MC-VI immobilized through hydrophobic interactions on a gold electrode coated with a nonpolar ...

Teicoplanin is a glycopeptide antibiotic with activity against Gram-positive bacteria and remains one of the last lines of clinical defense against certain bacterial infections. We have cloned, expressed, and purified the cytochrome P450 OxyE (CYP165D3) from the teicoplanin biosynthetic gene cluster of Actinoplanes teichomyceticus, which is responsible for the phenolic ...

HO-2 oxidizes heme to CO and biliverdin; the latter is reduced to bilirubin by biliverdin reductase (BVR). In addition, HO-2 is a redox-sensitive K/Ca(2)-associated protein, and BVR is an S/T/Y kinase. The two enzymes are components of cellular defense mechanisms. This is the first reporting of regulation of HO-2 by ...

Histidine-heme loop formation in the denatured state of a protein is a sensitive means for probing residual structure under unfolding conditions. In this study, we use a host-guest approach to investigate the relative tendencies of different amino acids to promote residual structure under denaturing conditions. The host for this work ...

Changes in the secondary structure of cytochrome c on immersion in methanol were monitored using circular dichroism. These changes occurred immediately in methanol, upon re-immersion in aqueous buffer, the secondary structure was restored in ca. 45 min. This method enables the secondary structure of proteins in non-aqueous solvents to be ...

Cytochrome c (cyt c) is a stable protein that functions in a monomeric state as an electron donor for cytochrome c oxidase. It is also released to the cytosol when permeabilization of the mitochondrial outer membrane occurs at the early stage of apoptosis. For nearly half a century, it has ...

Cholesterol oxidase is of significant commercial interest as it is widely used as a biosensor for the detection of cholesterol in clinical samples, blood serum and food. Increased stability of this enzyme with regards to temperature and different solvent conditions are of great importance to the reliability and versatility of ...

The site(s) of interaction between human cytochrome P450 2B6 and NADPH-cytochrome P450 reductase (P450 reductase) have yet to be identified. To investigate this, the cross-linking agent 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC) was used to covalently link P450 2B6-P450 reductase. Following digestion with trypsin, the cross-linked peptides were identified by reconstituting the peptides ...