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Diorganolellurides efficiently catalyze the aerobic oxidation of organosilanes under photosensitized conditions to afford the corresponding silanols in excellent yield. [ABSTRACT FROM AUTHOR]

Organotellurium compounds are known to be useful oxidation reagents. For developing a recoverable and reusable reagent, this paper describes the use of an ionic liquid (IL) support for the organotellurium reagent and its application as a recyclable catalyst for thiol oxidation. We have successfully prepared a novel diphenyl telluride derivative 5 bearing an imidazolium hexafluorophosphate group in its structure. It is found that the IL-supported diphenyl telluride 5 efficiently catalyzed the aerobic oxidation of various thiols in [bmim]PF6 solution under photosensitized conditions to provide the corresponding disulfides in excellent yields. The product can be isolated by simple ether extraction. The IL-supported catalyst 5 remaining in the ionic liquid phase can be reused for five successive runs while retaining high catalytic activity (97% yield even in the fifth run). [ABSTRACT FROM AUTHOR]

Abstract: A novel [2.2]metacyclophane in which two benzene rings are linked together with a carbon–carbon double bond and a disilane unit was prepared. Photolysis of the cyclophane in the presence of oxygen afforded the 4,5-dihydro-4,5-disilapyrene derivative via a transannular dehydrogenation reaction. [Copyright &y& Elsevier]

Only two crystal structures of diorganotellurones have been reported to date, both of which contain cocrystallized solvents and one of which is stabilized by intramolecular Te—N secondary bonding interactions. This work describes the crystal structure of bis(2,6‐diisopropylphenyl) tellurone, (C12H17)2TeO2 or C24H34O2Te, the first well‐defined diorganotellurone without cocrystallized solvents and without stabilizing intramolecular contacts. The molecule has crystallographic twofold symmetry, with half the molecule as the asymmetric unit. The molecular structure is compared to previously reported tellurones and those computed at the density functional theory DFT/B3PW91 level. The molecules form two‐dimensional layers as a result of a weak intermolecular hydrogen‐bonding network. The layers are then stacked in an antiparallel manner to form the crystal packing structure. The Hirshfeld surface analysis was employed to visualize and quantify the intermolecular contacts in the molecular crystal structure, and the contribution of O...H and H...H interactions was found to be the dominating factor. [ABSTRACT FROM AUTHOR]

C36H26Te, orthorhombic, Pca21 (no. 29), a = 13.5004(4) Å, b = 13.5677(3) Å, c = 14.2006(4) Å, V = 2601.12(12) Å3, Z = 4, Rgt(F) = 0.0247, wRref(F2) = 0.0530, T = 93 K. [ABSTRACT FROM AUTHOR]

Foldamers, which are folded oligomers with well-defined conformations, have been recently reported to have a good cell-penetrating ability. α,α-Disubstituted α-amino acids are one such promising tool for the design of peptide foldamers. Here, we prepared four types of L-arginine-rich nonapeptides containing L-leucine or α,α-disubstituted α-amino acids, and evaluated their secondary structures and cell-penetrating abilities in order to elucidate a correlation between them. Peptides containing α,α-disubstituted α-amino acids had similar resistance to protease digestion but showed different secondary structures. Intracellular uptake assays revealed that the helicity of peptides was important for their cell-penetrating abilities. These findings suggested that a peptide foldamer with a stable helical structure could be promising for the design of cell-penetrating peptides. [ABSTRACT FROM AUTHOR]

Organ‐selective targeting of mRNA polyplexes has been rarely explored despite the substantial potential of polymer‐based systems in mRNA delivery. In this study, spleen‐selective delivery of polyplexes is achieved by employing mRNA engineering to coat them with poly(ethylene glycol) (PEG). In this approach, mRNA is hybridized with PEGylated complementary RNA oligonucleotides (PEG–OligoRNAs), followed by the addition of linear poly(ethyleneimine). In this method, it is ensured that nearly all added PEG strands bind to the polyplexes, thereby enabling precise control of PEG amounts on the surface. Following systemic injection into mice, non‐PEGylated polyplexes yield robust protein expression in the lung and spleen. Intriguingly, adding a small number of PEG–OligoRNAs drastically reduces protein expression efficiency in the lung while preserving it in the spleen, realizing spleen targeting of mRNA polyplexes. Furthermore, PEGylated polyplexes demonstrate their potential utility in mRNA vaccination. In mechanistic analyses, non‐PEGylated polyplexes immediately agglomerate in the blood and deposit in the lung. Coating polyplexes with a small amount of short PEG effectively prevents these processes. Notably, even slight changes in PEG amounts and lengths dramatically impact the physicochemical properties and biological functionalities of the polyplexes, emphasizing the benefits of an mRNA engineering‐based approach for fine‐tuning polyplex PEG coating. [ABSTRACT FROM AUTHOR]

C16H25F3O5STe, monoclinic, P21/c (no. 14), a = 5.8214(2) Å, b = 16.0059(5) Å, c = 21.9311(7) Å, β = 94.760(3)°, V = 2036.42(12) Å3, Z = 4, Rgt(F) = 0.0282, wRref(F2) = 0.0598, T = 293 K. [ABSTRACT FROM AUTHOR]

We have designed and synthesized a set of cell-penetrating foldamers (CPFs), Blocks 1–8, composed of the common amino acids Leu, Arg, and Gly, as well as the helicogenic amino acid 2-aminoisobutyric acid. The findings showed that Block 3 could deliver siRNA into cells without significant cytotoxicity. We also demonstrated that Block 3 could be applied to selectively kill the oncogene-driven cancer cells. [ABSTRACT FROM AUTHOR]

[Display omitted] Nanoparticle-based delivery systems have contributed to the recent clinical success of RNA therapeutics, including siRNA and mRNA. RNA delivery using polymers has several distinct properties, such as enabling RNA delivery into extra-hepatic organs, modulation of immune responses to RNA, and regulation of intracellular RNA release. However, delivery systems should overcome safety and stability issues to achieve widespread therapeutic applications. Safety concerns include direct damage to cellular components, innate and adaptive immune responses, complement activation, and interaction with surrounding molecules and cells in the blood circulation. The stability of the delivery systems should balance extracellular RNA protection and controlled intracellular RNA release, which requires optimization for each RNA species. Further, polymer designs for improving safety and stability often conflict with each other. This review covers advances in polymer-based approaches to address these issues over several years, focusing on biological understanding and design concepts for delivery systems rather than material chemistry. [ABSTRACT FROM AUTHOR]

Several protein transfection reagents are commercially available and are powerful tools for elucidating function of a protein in a cell. Here we described protein transfection studies of the commercially available reagents, Pro-DeliverIN, Xfect, and TuboFect, using Huh-7 multicellular tumor spheroid (MCTS) as a three-dimensional in vitro tumor model. A cellular uptake study using specific endocytosis inhibitors revealed that each reagent was internalized into Huh-7 MCTS by different mechanisms, which were the same as monolayer cultured Huh-7 cells. A certain amount of Pro-DeliverIN and Xfect was uptaken by Huh-7 cells through caveolae-mediated endocytosis, which may lead to transcytosis through the surface-first layered cells of MCTS. The results presented here will help in the choice and use of protein transfection reagents for evaluating anti-tumor therapeutic proteins against MCTS models. [ABSTRACT FROM AUTHOR]

Abstract: l–Leu‐based heteropeptides having (R)‐ or (S)‐chiral five‐membered carbocyclic ring amino acids (Ac5c3EG) with an ethylene acetal moiety were prepared. A conformational analysis using FT‐IR absorption, 1H NMR, and circular dichroism (CD) spectra revealed that l–Leu‐based hexapeptides and nonapeptides having (R)‐ or (S)‐Ac5c3EG formed right‐handed (P) helical structures in solution. An X‐ray crystallographic analysis of nonapeptides 5 a and 5 b showed similar right‐handed (P) α‐helical structures, without an intramolecular hydrogen bond of the peptide N–H⋅⋅⋅–O– (acetal) type. [ABSTRACT FROM AUTHOR]

Cell-penetrating peptides (CPP) have attracted many scientists’ attention as intracellular delivery tools due to their high cargo molecule transportation efficiency and low cytotoxicity. Therefore, in many research fields CPP, such as HIV-Tat and oligoarginine (Rn), are used to deliver hydrophilic drugs and biomolecules, including proteins, DNA, and RNA. We designed four types of CPP that contained cationic α,α-disubstituted amino acids (Api C2Gu and Api C4Gu ) as helical promoters; i.e., 1 – 4 [FAM-β-Ala-( l -Arg- l -Arg-Xaa) 3 -(Gly) 3 -NH 2 ( 1 : Xaa = Api C2Gu , 2 : Xaa = Api C4Gu ), 3 : FAM-β-Ala-( l -Arg) 8 -Api C2Gu -(Gly) 3 -NH 2 , and 4 : FAM-β-Ala-( l -Arg) 5 -Api C2Gu -( l -Arg) 2 -Api C2Gu -(Gly) 3 -NH 2 ], and investigated their preferred secondary structures and cell membrane-penetrating ability. As a result, we found that the permeation efficiency of the CPP was affected by the number of helical promoters in their sequences. Specially, peptide 1 , which contained three Api C2Gu residues, formed a stable helical structure and passed through the cell membrane more efficiently than the other peptides. Moreover, it was demonstrated that the spatial arrangement of the peptides’ side chains also influenced their permeability and the helical stabilization of their main chains. [ABSTRACT FROM AUTHOR]

l -Leu-based peptides having chiral six-membered ring amino acids: Boc-{ l -Leu- l -Leu-[(1 R ,3 R )- or (1 S ,3 R )-Ac 6 c 3M ]} n -OMe [n=1 ( 2 ), 2 ( 4 ), 3 ( 5 )], were synthesized. A conformational analysis using FTIR absorption and NOESY NMR spectra revealed that these hexa- and nonapeptides having (1 R ,3 R )-Ac 6 c 3M or (1 S ,3 R )-Ac 6 c 3M formed helical structures in CDCl 3 solution, while that using CD spectra suggested that the nonapeptide 5b having (1 S ,3 R )-Ac 6 c 3M become more right-handed ( P ) α-helical than the nonapeptide 5a having (1 R ,3 R )-Ac 6 c 3M in TFE solution. An X-ray crystallographic analysis showed that the hexapeptide 4b having (1 S ,3 R )-Ac 6 c 3M formed a partially distorted right-handed ( P ) 3 10 -/α-helical structure in the crystal state, while the nonapeptides 5a and 5b having (1 R ,3 R )-Ac 6 c 3M or (1 S ,3 R )-Ac 6 c 3M formed similar right-handed ( P ) α-helical backbone structures. [ABSTRACT FROM AUTHOR]

Two diastereomeric six-membered ring α,α-disubstituted α-amino acids (1 R ,3 R )- and (1 S ,3 R )-1-amino-3-methylcyclohexanecarboxylic acids (Ac 6 c 3M ); side-chain restricted leucine analogs, were stereoselectively synthesized from (3 R )-3-methylcyclohexanone by a Bucherer–Bergs or Strecker reaction. Two series of homo-chiral homopeptides Cbz-[(1R,3 R )- and (1S,3 R )-Ac 6 c 3M ] n -OMe, up to hexapeptides ( n =6), were prepared, respectively, and the preferred conformations of cyclohexane rings of amino acid residues and the peptide-backbones were studied. In solution, these peptides formed helical structures, but the helical-screw control to one-handedness was not possible for the hexapeptide length. In the crystal state, all (1 R ,3 R )-Ac 6 c 3M residues formed cyclohexane chair form conformations with a 3-methyl substituent at equatorial orientation and an amino group at the axial position, whereas all (1 S ,3 R )-Ac 6 c 3M residues assumed cyclohexane chair forms with the 3-methyl and amino groups at equatorial orientations. The preferred peptide-backbone structure of (1 R ,3 R )-Ac 6 c 3M hexapeptide had ( P ) and ( M ) 3 10 -helices, and that of (1 S ,3 R )-Ac 6 c 3M hexapeptide had ( P ) and ( M ) α-helices in the crystal state. [ABSTRACT FROM AUTHOR]

[Display omitted] Histone H2A mono-ubiquitination plays important roles in epigenetic gene expression and is also involved in tumorigenesis. Small molecules controlling H2A ubiquitination are of interest as potential chemical tools and anticancer drugs. To identify novel small molecule inhibitors of H2A ubiquitination, we synthesized and evaluated several compounds designed based on PRT4165 (1), which is a reported histone ubiquitin ligase RING1A inhibitor. We found that compound 11b strongly inhibited the viability and reduced histone H2A mono-ubiquitination in human osteosarcoma U2OS cells. Therefore, compound 11b is a promising lead compound for the development of H2A histone ubiquitination-inhibiting small molecules. [ABSTRACT FROM AUTHOR]

We developed a first-in-class proteolysis targeting chimera (PROTAC) for selective degradation of histone deacetylase 8 (HDAC8). The PROTAC induced degradation of HDAC8 without affecting the levels of other HDACs in cellular assays, and inhibited the growth of T-cell leukemia Jurkat cells more potently than a conventional HDAC8 inhibitor. [ABSTRACT FROM AUTHOR]

Fabrication of monodispersed, submicrometer-sized vesicles (nanosomes) that form through self-assembly possessing a thin and permeable membrane remains a significant challenge. Conventional fabrication of nanosomes through self-assembly of amphiphilic molecules often requires cumbersome processes using organic solvents combined with physical procedures (e.g., sonication, thermal treatment, and membrane filtration) to obtain unilamellar structures with a controlled size distribution. Herein, we report the first example of spontaneously formed submicrometer-sized unilamellar polyion complex vesicles (Nano- PlCsomes) via self-assembly of a pair of oppositely charged PEG block aniomer and homocatiomer in an aqueous medium. Detailed dynamic light scattering and transmission electron microscopic analysis revealed that vesicle sizes can be controlled in the range of 100-400 nm with a narrow size distribution, simply by changing the total polymer concentration. Also, each Nano-PlCsome was composed of a uniform single PlC membrane, the thickness of which is around 10-15 nm, regardless of its size. Fluorescence correlation spectroscopy measurement verified that Nano-PlCsomes were able to encapsulate water-soluble fluorescent macromolecules in the inner water phase and release them slowly into the exterior. Moreover, cross-linking of the vesicle membrane allows tuning of permeability, enhancement in stability under physiological conditions, and preservation of size and structure even after freeze-drying and centrifugation treatment. Finally, Nano-PlCsomes showed a long circulation time in the bloodstream of mice. Precise control of the particle size and structure of hollow capsules through simple aqueous self-assembly and easy modification of their properties by cross-linking is quite novel and fascinating in terms of ecological, low-cost, and low-energy fabrication processes as well as the potential utility in the biomedical arena. [ABSTRACT FROM AUTHOR]

PEG-based polyplex micelles, which can detach the surrounding PEG chains responsive to the intracellular reducing environment, were developed as nonviral gene vectors. A novel block catiomer, PEG-SS-P[Asp(DET)], was designed as follows: (i) insertion of biocleavable disulfide linkage between PEG and polycation segment to trigger PEG detachment and (ii) a cationic segment based on poly(aspartamide) with a flanking N-(2-aminoethyl)-2-aminoethyl group, P[Asp(DET)], in which the Asp(DET) unit acts as a buffering moiety inducing endosomal escape with minimal cytotoxicity. The polyplex micelles from PEG-SS-P[Asp(DET)] and plasmid DNA (pDNA) stably dispersed in an aqueous medium with a narrowly distributed size range of ∼ 80 nm due to the formation of hydrophilic PEG palisades while undergoing aggregation by the addition of 10 mM dithiothreitol (DTT) at the stoichiometric charge ratio, indicating the PEG detachment from the micelles through the disulfide cleavage. The PEG-SS-P[Asp(DET)] micelles showed both a 1-3 orders of magnitude higher gene transfection efficiency and a more rapid onset of gene expression than PEG-P[Asp(DET)] micelles without disulfide linkages, due to much more effective endosomal escape based on the PEG detachment in endosome. These findings suggest that the PEG-SS-P[Asp(DET)] micelle may have promising potential as a nonviral gene vector exerting high transfection with regulated timing and minimal cytotoxicity. [ABSTRACT FROM AUTHOR]

Cell-penetrating peptides (CPPs) are an attractive tool for delivering membrane-impermeable compounds, including anionic biomacromolecules such as DNA and RNA, into living cells. Amphipathic helical peptides composed of hydrophobic amino acids and cationic amino acids are typical CPPs. In the current study, we designed amphipathic helical 12-mer peptides containing α,α-disubstituted α-amino acids (dAAs), which are known to stabilize peptide secondary structures. The dominant secondary structures of peptides in aqueous solution differed according to the introduced dAAs. Peptides containing hydrophobic dAAs and adopting a helical structure exhibited a good cell-penetrating ability. As an application of amphipathic helical peptides, small interfering RNA (siRNA) delivery into living human hepatoma cells was investigated. One of the peptides containing dAAs dipropylglycine formed stable complexes with siRNA at appropriate zeta-potential and size for intracellular siRNA delivery. This peptide showed effective RNA interference efficiency at short peptide length and low concentrations of peptide and siRNA. These findings will be helpful for the design of amphipathic helical CPPs as intracellular siRNA delivery. [ABSTRACT FROM AUTHOR]

Various racemic α‐trifluoromethyl α,α‐disubstituted α‐amino acids were synthesized by the reaction of methyl 3,3,3‐trifluoropyruvate imines with Grignard reagents. The optical resolution of racemates using (R)‐1,1'‐bi‐2‐naphthol {(R)‐BINOL} esters gave optically active α‐trifluoromethylated α,α‐disubstituted α‐amino acids, such as α‐trifluoromethylalanine (αCF3Ala), α‐trifluoromethylleucine (αCF3Leu), and α‐trifluoromethylphenylalanine (αCF3Phe). The optically active (R)‐ or (S)‐αCF3Ala was incorporated into the L–Leu‐based pentapeptides, and their preferred conformation in solution and in the crystal state was studied by Fourier transform infrared (FT‐IR) absorption, nuclear Overhauser effect spectroscopy (NOESY) NMR, and circular dichroism (CD) spectra, as well as X‐ray crystallographic analysis. Both L–Leu‐based peptides with (R)‐ or (S)‐αCF3Ala formed right‐handed 310‐helical structures. Both peptide‐backbones at the N‐terminal residues 1–3 were very similar, but the φ and ψ torsion angles of residues 4 and 5 between peptides with (R)‐ or (S)‐ αCF3Ala were different. [ABSTRACT FROM AUTHOR]

We describe the synthesis of an ionic-liquid (IL)-supported organotelluride catalyst and its application as a recyclable catalyst for the aerobic oxidation of phosphite esters to phosphate esters. This method shows high conversion rates, allows the ready isolation and purification of the resulting products, and exhibits good reusability of the catalyst. [ABSTRACT FROM AUTHOR]

Both efficiency and safety profiles are crucial for promotion of gene delivery systems towards practical applications. A promising template system was previously developed based on block catiomer of poly(ethylene glycol) (PEG)- b -poly{N′-[ N -(2-aminoethyl)-2-aminoehtyl]aspartamide}-cholesteryl [PEG-PAsp(DET)-cholesteryl] with strategies of ligand conjugation at the α-terminus for specific affinity to the targeted cells and cholesteryl conjugation at the ω-terminus for structural stabilization to obtain systemic retention. Aiming for advocating this formulation towards practical applications, in the current study, the binding profile of this polymer to plasmid DNA (pDNA) was carefully studied to address an issue of toxicity origin. Quantification of free polymer composition confirmed that the toxicity mainly results from unbound polymer and polyplex micelle itself has negligible toxicity. This evaluation allowed for identifying an optimal condition to prepare safe polyplex micelles for systemic application that possess maximal polymer-binding but exclude free polymers. The identified polyplex micelles then faced a drawback of limited transfection efficiency due to the absence of free polymer, which is an acknowledged tendency found in various synthetic gene carriers. Thus, series of functional components was strategically compiled to improve the transfection efficiency such as attachment of cyclic (Arg-Gly-Asp) (cRGD) peptide as a ligand onto the polyplex micelles to facilitate cellular uptake, use of endosome membrane disruptive catiomer of PAsp(DET) for facilitating endosome escape along with use of the conjugated cholesteryl group to amplify the effect of PAsp(DET) on membrane disruption, so as to obtain efficient transfection. The mechanistic investigation respecting the appreciated pH dependent protonation behavior of PAsp(DET) permitted to depict an intriguing scenario how the block catiomers manage to escape from the endosome entrapment in response to the pH gradient. Subsequent systemic application to the pancreatic tumor demonstrated a capability of vascular targeting mediated by the cRGD ligand, which was directly confirmed based on in situ confocal laser scanning microscopy observation. Encouraging this result, the vascular targeting to transfect a secretable anti-angiogenic gene was attempted to treat the intractable pancreatic tumor with anticipation that the strategy could circumvent the intrinsic physiological barriers derived from hypovascular and fibrotic characters. The obtained therapeutic efficiency demonstrates promising utilities of the proposed formulation as a safe systemic gene delivery carrier in practical use. [ABSTRACT FROM AUTHOR]

[Display omitted] AMP deaminase 2 (AMPD2) has been thought to play an important role in energy homeostasis and immuno-oncology, while selective AMPD2 inhibitors are highly demanded to clarify the physiological function of AMPD2. In this report, we describe selective AMPD2 inhibitors inducing allosteric modulation. Based on hypothesis that compounds that exhibit increased inhibition by preincubation would cause conformational change of the enzyme, starting from HTS hit compound 4 , we discovered compound 8 through the SAR study. From X-ray structural information of 8 , this chemical series has a novel mechanism of action that changes the substrate pocket to prevent AMP from binding. Further elaboration of compound 8 led to the tool compound 21 which exhibited potent inhibitory activity of AMPD2 in ex vivo evaluation of mouse liver. [ABSTRACT FROM AUTHOR]

Cell-penetrating peptides (CPPs) have been developed as drug, protein, and gene delivery tools. In the present study, arginine (Arg)-rich CPPs containing unnatural amino acids were designed to deliver plasmid DNA (pDNA). The transfection ability of one of the Arg-rich CPPs examined here was more effective than that of the Arg nonapeptide, which is the most frequently used CPP. The transfection efficiencies of Arg-rich CPPs increased with longer post-incubation times and were significantly higher at 48-h and 72-h post-incubation than that of the commercially available transfection reagent TurboFect. These Arg-rich CPPs were complexed with pDNA for a long time in cells and effectively escaped from the late endosomes/lysosomes into the cytoplasm. These results will be helpful for designing novel CPPs for pDNA delivery. [ABSTRACT FROM AUTHOR]

We investigated the preferred conformations of l-Leu-Aib-alternating peptides, Boc-( l-Leu-Aib) n-OMe ( n = 1: 1, 2: 2, 3: 3, 4: 4, 5: 5), in solution and in the crystalline state. Peptides that contain more than six amino acid residues fold into right-handed ( P) helical structures. Specifically, hexapeptide 3 forms a ( P) 310-helix, and octapeptide 4 and decapeptide 5 form ( P) α-helices as their preferred conformations in solution. In the crystalline state, both octapeptide 4 and decapeptide 5 fold into ( P) α-helices. [ABSTRACT FROM AUTHOR]

A homochiral L-Leu- L-Leu-Aib segment was incorporated into the N- or C-termini of left-handed ( M) helical peptides ( D-Leu- L-Leu-Aib) n. We then investigated the preferred conformations of two sets of three peptides; i.e., Boc- L-Leu- L-Leu-Aib-( D-Leu- L-Leu-Aib) n-OMe ( n = 1: 1; 2: 2; 3: 3) and Boc-( D-Leu- L-Leu-Aib) n- L-Leu- L-Leu-Aib-OMe ( n = 1: 4; 2: 5; 3: 6), in solution and in the crystalline state. Nonapeptide 2 and dodecapeptide 3, each containing an N-terminal L-Leu- L-Leu-Aib segment, formed left-handed ( M) helices as the preferred secondary structures in solution. In the crystalline state, nonapeptide 2 folded into an ( M) α-helical structure. Peptides 4- 6, each containing a C-terminal L-Leu- L-Leu-Aib segment, formed roughly equivalent amounts of right-handed ( P) and ( M) helices. [ABSTRACT FROM AUTHOR]

[Display omitted] Arginine (Arg)-rich peptides can penetrate the cell membrane and deliver nucleic acid-based therapeutics into cells. In this study, a helical template designed with a repeating sequence composed of two l -leucines (l -Leu) and a 2-aminoisobutyric acid (Aib) (l -Leu- l -Leu-Aib) was conjugated to nona-arginine on either the C- or N- terminus, designated as Block 1 and Block 2. Each terminal modification induced helical structure formation and improved the physicochemical properties of peptide/plasmid DNA (pDNA) complexes, resulting in efficient intracellular pDNA delivery. The introduction of a helical template may be effective for the endosomal escape of pDNA and pDNA release from complexes in cells. These results emphasized the potency of a helical template for the development of novel cell-penetrating peptides for pDNA delivery. [ABSTRACT FROM AUTHOR]