A Lipid-Sensitive Spider Peptide Toxin Exhibits Selective Anti-Leukemia Efficacy through Multimodal Mechanisms.

Anti-cancer peptides (ACPs) represent a promising potential for cancer treatment, although their mechanisms need to be further elucidated to improve their application in cancer therapy. Lycosin-I, a linear amphipathic peptide isolated from the venom of Lycosa singorensis, shows significant anticancer potential. Herein, it is found that Lycosin-I, which can self-assemble into a nanosphere structure, has a multimodal mechanism of action involving lipid binding for the selective and effective treatment of leukemia.

Cu(BF)/AC-Catalyzed Synthesis of -Substituted Anilines, -Substituted 1,6-Naphthyridin-5(6)-one, and Isoquinolin-1(2)-one.

Herein, we report practical Cu(BF)/activated carbon-catalyzed amination of various anilines, isoquinolinone, and naphthyridinone with aryl boronic acids. The ultrasonic and rotary evaporation treatment of the mixture of aq. Cu(BF) and activated carbon in methanol afforded a novel Cu(II)-catalyst, which is air-stable and can be effectively applied in the Chan-Lam coupling reaction.

Peptide nanotube loaded with a STING agonist, c-di-GMP, enhance cancer immunotherapy against melanoma.

Unlabelled: The activation of the stimulating factor of the interferon gene (STING) pathway can enhance the immune response within the tumor. Cyclic diguanylate monophosphate (c-di-GMP) is a negatively charged, hydrophilic STING agonist, however, its effectiveness is limited due to the poor membrane permeability and low bioavailability. Herein, we introduced KL-7 peptide derived from Aβ amyloid fibrils that can self-assemble to form nanotubes to load and deliver c-di-GMP, which significantly enhanced c-di-GMP's effectiveness and then exhibited a robust " immunity" to kill melanoma cells.

Structure-based discovery of potent inhibitors of Axl: design, synthesis, and biological evaluation.

Commonly overexpressed in many cancers and associated with tumor growth, metastasis, drug resistance, and poor overall survival, Axl has emerged as a promising target for cancer therapy. However, the availability of new chemical forms for Axl inhibition is limited. Herein, we present the development and characterization of novel Axl inhibitors, including the design, synthesis, and structure-activity relationships (SARs) of a series of diphenylpyrimidine-diamine derivatives.

Improvement of anticancer effect of berberine by salt formation modifications.

Background: Berberine is a quaternary isoquinoline alkaloid that possesses a significant therapeutic effect on a variety of cancers. However, due to poor bioavailability, an increased dose is often required to achieve therapeutic goals. To improve the activities of natural berberine, most modifications were focused on the positive isoquinoline unit by grafting long aliphatic chains or heterocycles.

Dual-sensitive antibacterial peptide nanoparticles prevent dental caries.

Dental caries is the most prevalent bacterial biofilm-induced disease. Current clinical prevention and treatment agents often suffer from adverse effects on oral microbiota diversity and normal tissues, predominately arising from the poor biofilm-targeting property of the agents. To address this concern, we herein report dual-sensitive antibacterial peptide nanoparticles pHly-1 NPs upon acid and lipid-binding for treatment of dental caries.

Small-molecule albumin ligand modification to enhance the anti-diabetic ability of GLP-1 derivatives.

Glucagon-like peptide-1 (GLP-1) receptor agonists modified with albumin ligands which can specificity bind to the human serum albumin (HSA) was an efficient strategy to prolong the half-time of GLP-1. Herein, we investigated the effect of small-molecule albumin ligand modification on the hypoglycemic activities of GLP-1 derivatives. Two GLP-1 derivatives MPA-C12-GLP-1 and Rhein-C12-GLP-1 were achieved by modification of the side chain amino of lysine in position 26 of the Arg34-GLP-1(7-37)-OH with Rhein and 3-Maleimidopropionic acid respectively using 12-aminolauric acid as a linker, and its specific albumin-conjugating characteristics, pharmaceutical characterization, and the antidiabetic effects were investigated.

Evaluation of pentaerythritol-based and trimethylolpropane-based cationic lipidic materials for gene delivery.

The chemical and physical structure of cationic liposomes pays an important effect on their gene transfection efficiency. Investigation on the structure-function relationship of cationic liposomes will guide the design of novel cationic liposomes with high transfection efficiency and biosafety. In this paper, two novel series of lipids based on the backbone of pentaerythritol and trimethylolpropane were discovered, and their gene transfection efficiencies were assayed in vitro.

Fatty Acid Modification of the Anticancer Peptide LVTX-9 to Enhance Its Cytotoxicity against Malignant Melanoma Cells.

Spider venom is a valuable resource for the development of novel anticancer drugs. In this study, we focused on novel linear amphipathic α-helical anticancer peptide LVTX-9, which was derived from the cDNA library of the venom gland of the spider . The cytotoxicity of LVTX-9 against murine melanoma cells in the range of 1.

Glucose-Lipopeptide Conjugates Reveal the Role of Glucose Modification Position in Complexation and the Potential of Malignant Melanoma Therapy.

Glycosylation and fatty acid modification are promising strategies to improve peptide performance. We previously studied glycosylation and fatty acid modification of the anticancer peptide R-lycosin-I. In this study, we further investigated the co-modification of fatty acids and monosaccharides in R-lycosin-I.

Drug-Bearing Peptide-Based Nanospheres for the Inhibition of Metastasis and Growth of Cancer.

Employing a peptide-based nanoscale drug delivery system is an effective strategy to overcome the poor therapeutic outcomes of chemotherapeutic drugs. Here, we developed a self-assembling peptide-drug delivery system comprising a self-assembling anticancer peptide (R-lycosin-I), as revealed in our previous study, and 10-hydroxycamptothecin (HCPT) for cancer therapy. The results showed that peptide-drug conjugates (R-L-HCPT) could assemble into nanospheres of 40-60 nm in water.

Position Effect of Fatty Acid Modification on the Cytotoxicity and Antimetastasis Potential of the Cytotoxic Peptide Lycosin-I.

Peptide modification with fatty acids is an effective method to improve peptide performance. We previously investigated the fatty acid modification of R-lycosin-I, a cytotoxic peptide derived from lycosin-I from the venom of the spider . In this study, we further investigated the position effects of fatty acid modification of lycosin-I.

Monosaccharide Analogues of Anticancer Peptide R-Lycosin-I: Role of Monosaccharide Conjugation in Complexation and the Potential of Lung Cancer Targeting and Therapy.

Glycoconjugation is a promising modification strategy for the optimization of peptide drugs. In this study, five different monosaccharide derivatives () were covalently linked to the N-terminal of R-lycosin-I, which yielded five glycopeptides (). They demonstrated increased or reduced cytotoxicity depending on monosaccharide types, which might be explained by the changes of physicochemical properties.

The Roles of Fatty-Acid Modification in the Activity of the Anticancer Peptide R-Lycosin-I.

We previously reported that R-lycosin-I, modified by amino acid substitution from lycosin-I, was a peptide with anticancer activity and a linear amphipathic α-helix conformation and that it can induce cancer cell apoptosis and inhibit cell proliferation. However, the anticancer activity of R-lycosin-I was not highly improved. In order to further improve the anticancer activity of R-lycosin-I, fatty acids with different chain lengths from 12 to 20 carbons were introduced to the N-terminal of R-lycosin-I to yield five lipopeptides (R-C, R-C, R-C, R-C, R-C).

Fabrication of Positively Charged Fluorescent Polymer Nanoparticles for Cell Imaging and Gene Delivery.

Development of efficient non-viral gene delivery vector has aroused great attention in the past few decades. In this study, we reported a new gene delivery vector, positively charged fluorescent conjugated polymer nanoparticles (CPNPs), for efficient gene transfection and in-situ intracellular fluorescence imaging. The microscopic and spectroscopic characterizations demonstrated that these CPNPs possess decent fluorescence performance (e.

Arginine modification of lycosin-I to improve inhibitory activity against cancer cells.

Lycosin-I is a linear amphipathic α-helical anticancer peptide (ACP) extracted from the spider Lycosa singoriensis, which can activate the mitochondrial death pathway to induce apoptosis in tumor cells and up-regulate p27 to inhibit cell proliferation. However, the applicability of lycosin-I as a novel anticancer drug is limited by its low cellular entry and efficacy in solid tumors. Amino acid substitution presents an effective and modest strategy to improve the anticancer activity and bioavailability of ACPs.

Synthesis and evaluation of L-arabinose-based cationic glycolipids as effective vectors for pDNA and siRNA in vitro.

Glycolipids might become a new type of promising non-viral gene delivery systems because of their low cytotoxicity, structural diversity, controllable aqua- and lipo-solubility, appropriate density and distribution of positive charges, high transfer efficiency and potential targeting function. In this study, four kinds of L-arabinose-based cationic glycolipids (Ara-DiC12MA, Ara-DiC14MA, Ara-DiC16MA and Ara-DiC18MA) containing quaternary ammonium as hydrophilic headgroup and two alkane chains as hydrophobic domain were synthesized and characterized. They were observed to have strong affinities for plasmid DNA (pDNA) and siRNA, the pDNA can be completely condensed at N/P ratio less than 2, and the siRNA can be completely retarded at N/P ratio less than 3.

Evaluation of Maltose-Based Cationic Liposomes with Different Hydrophobic Tails for Plasmid DNA Delivery.

In this paper, three cationic glycolipids with different hydrophobic chains Malt-DiC12MA (), Malt-DiC14MA () and Malt-DiC16MA () were constructed by using maltose as starting material via peracetylation, selective 1--deacetylation, trichloroacetimidation, glycosylation, azidation, deacetylation, Staudinger reaction, tertiary amination and quaternization. Target compounds and some intermediates were characterized by ¹H-NMR, C-NMR, ¹H-¹H COSY and ¹H-C HSQC. The results of gel electrophoresis assay, atomic force microscopy images (AFM) and dynamic light scattering (DLS) demonstrate that all the liposomes could efficiently bind and compact DNA (N/P ratio less than 2) into nanoparticles with proper size (88 nm-146 nm, PDI < 0.

Design, synthesis and in vitro evaluation of d-glucose-based cationic glycolipids for gene delivery.

A cationic lipid consists of a hydrophilic headgroup, backbone and hydrophobic tails which have an immense influence on the transfection efficiency of the lipid. In this paper, two novel series of cationic cyclic glycolipids with a quaternary ammonium headgroup and different-length hydrophobic tails (dodecyl, tetradecyl, hexadecyl) have been designed and synthesized for gene delivery. One contains lipids 1-3 with two hydrophobic alkyl chains linked to the glucose ring directly via an ether link.

Pd-catalyzed desymmetric intramolecular O-arylation reaction: enantioselective synthesis of (3,4-dihydro-2H-chromen-3-yl)methanols.

An enantioselective intramolecular O-arylation was achieved through desymmetrization with Pd-catalyzed coupling reactions. The intramolecular asymmetric aryl C-O coupling reactions of 2-(2-haloaryl)propane-1,3-diols led to the enantioselective formation of chiral (3,4-dihydro-2H-chromen-3-yl)methanols in good yields and high enantiomeric selectivity.

Copper-catalyzed enantioselective intramolecular N-arylation, an efficient method for kinetic resolutions.

For the first time, copper-catalyzed intramolecular N-arylation was successfully applied to the kinetic resolution strategy. Under the catalysis of CuI-BINOL derived ligands, the kinetic resolution of rac-2-amino-3-(2-iodoaryl)propionates and rac-2-amino-4-(2-iodoaryl)butanoates afforded chiral intramolecular coupling products and recovered the starting materials in high enantioselectivity (s factors up to 245).

Pd-catalyzed one-pot synthesis of polysubstituted acrylamidines from isocyanides, diazo compounds, and imines.

A novel and efficient Pd-catalyzed one-pot reaction of ethyl diazoacetate, isocyanides, and imines for the synthesis of acrylamidines was developed. The multicomponent reaction may have occurred through an unpredicted ring-opening process of the ketenimine-imine [2 + 2] intermediate to form the acrylamidine products.

Pre-activation based stereoselective glycosylations: Stereochemical control by additives and solvent.

Stereochemical control is an important issue in carbohydrate synthesis. Glycosyl donors with participating acyl protective groups on 2-O have been shown to give 1,2-trans glycosides reliably under the pre-activation based reaction condition. In this work, the effects of additives and reaction solvents on stereoselectivity were examined using donors without participating protective groups on 2-O.

[One-stage phallic reconstruction with extended pudendal-thigh flap: a desirable surgical option].

Objective: To investigate the feasibility of one-stage phallic reconstruction with the extended pudendal-thigh flap (EPTF) to achieve a higher survival rate, shorter surgical cycle, and more experimental evidence for the clinical application of the technique.

Methods: We equally randomized 36 healthy adult New Zealand rabbits to an experimental and a control group to receive one-stage phallic reconstruction, the former with EPTF (pudendal-thigh flap + thigh cutaneous branches of the superficial external pudendal artery, PTF + TCB), the urethra reconstructed with the TCB flap, and the latter with bilateral pudendal-thigh flaps.

Results: The survival rate of the reconstructed phallus was 83.