Impact of N-Terminal PEGylation on Synthesis and Purification of Peptide-Based Cancer Epitopes for Pancreatic Ductal Adenocarcinoma (PDAC).

Peptide-based cancer vaccines have shown promising results in preclinical trials focusing on tumor immunotherapy. However, the presence of hydrophobic amino acid segments within these peptide sequences poses challenges in their synthesis, purification, and solubility, thereby hindering their potential use as cancer vaccines. In this study, we successfully synthesized peptide sequences derived from mesothelin (MSLN), a tumor-associated antigen overexpressed in pancreatic ductal adenocarcinoma (PDAC) by conjugating them with monodisperse polyethylene glycol (PEG).

Differential Detection of Amyloid Aggregates in Old Animals Using Gold Nanorods by Computerized Tomography: A Pharmacokinetic and Bioaccumulation Study.

Introduction: The development of new materials and tools for radiology is key to the implementation of this diagnostic technique in clinics. In this work, we evaluated the differential accumulation of peptide-functionalized GNRs in a transgenic animal model (APPswe/PSENd1E9) of Alzheimer's disease (AD) by computed tomography (CT) and measured the pharmacokinetic parameters and bioaccumulation of the nanosystem.

Methods: The GNRs were functionalized with two peptides, Ang2 and D1, which conferred on them the properties of crossing the blood-brain barrier and binding to amyloid aggregates, respectively, thus making them a diagnostic tool with great potential for AD.

Pharmacological activation of insulin-degrading enzyme improves insulin secretion and glucose tolerance in diet-induced obese mice.

Aim: To investigate the use of synthetic preimplantation factor (sPIF) as a potential therapeutic tool for improving glucose-stimulated insulin secretion (GSIS), glucose tolerance and insulin sensitivity in the setting of diabetes.

Materials And Methods: We used a preclinical murine model of type 2 diabetes (T2D) induced by high-fat diet (HFD) feeding for 12 weeks. Saline or sPIF (1 mg/kg/day) was administered to mice by subcutaneously implanted osmotic mini-pumps for 25 days.

Evaluation of the tert-butyl group as a probe for NMR studies of macromolecular complexes.

The development of methyl transverse relaxation optimized spectroscopy has greatly facilitated the study of macromolecular assemblies by solution NMR spectroscopy. However, limited sample solubility and stability has hindered application of this technique to ongoing studies of complexes formed on membranes by the neuronal SNAREs that mediate neurotransmitter release and synaptotagmin-1, the Ca sensor that triggers release. Since the H NMR signal of a Bu group attached to a large protein or complex can be observed with high sensitivity if the group retains high mobility, we have explored the use of this strategy to analyze presynaptic complexes involved in neurotransmitter release.

Amide Formation: Choosing the Safer Carbodiimide in Combination with OxymaPure to Avoid HCN Release.

It has been reported that DIC can react with OxymaPure to render an oxadiazole compound with the concomitant formation of HCN. Here we demonstrate that this reaction is not a feature of all carbodiimides but rather depends on the alkyl structure that flanks the two N atoms of the carbodiimide. Furthermore, we have identified two carbodiimides, TBEC and EDC·HCl, whose reaction with OxymaPure is exempt from HCN formation.

Solid-Phase Synthesis of Head to Side-Chain Tyr-Cyclodepsipeptides Through a Cyclative Cleavage From Fmoc-MeDbz/MeNbz-resins.

Cyclic depsipeptides constitute a fascinating class of natural products. Most of them are characterized by an ester formed between the β-hydroxy function of Ser/Thr -and related amino acids- and the carboxylic group of the -terminal amino acid. Less frequent are those where the thiol of Cys is involved rendering a thioester (cyclo thiodepsipeptides) and even less common are the cyclo depsipeptides with a phenyl ester coming from the side-chain of Tyr.

Exploring the influence of Diels-Alder linker length on photothermal molecule release from gold nanorods.

We studied the photothermal release of carboxyfluorescein (CF) linked to the gold surface of gold nanorods (GNRs) by two Diels-Alder adducts of different lengths (n = 4 and n = 9). The functionalized GNRs were irradiated with infrared light to produce photothermal release of CF by a retro-Diels-Alder reaction. The adducts were chemisorbed on the GNRs and the functionalized nanoparticles were characterized by UV-vis, DLS, zeta potential and Raman and surface-enhanced Raman spectroscopy (SERS).

Gold nanoparticles as an efficient drug delivery system for GLP-1 peptides.

In this work, the potential application of gold nanoparticles for GLP-1 analogues delivery was studied. For this purpose, the original sequence of the incretin GLP-1 was slightly modified in the C-terminal region by adding a cysteine residue to facilitate conjugation to the gold surface. The interaction between peptides and gold nanoparticles and also the colloid stability of the conjugates were studied by UV-vis spectrophotometry, TEM, IR and XPS spectroscopy.

Synthesis and Biological Evaluation of a Teixobactin Analogue.

The first synthesis and biological activity of a teixobactin analogue is reported. Substitution of the unusual L-allo-enduracididine residue by the naturally occurring L-arginine was achieved, and the analogue gave an activity trend similar to that of teixobactin (against Gram-postive bacteria) and meropenem, which was approved by the FDA in 1996. The synthetic route used allows for the synthesis of the natural product as well as the development of a program of medicinal chemistry.

2-Methyltetrahydrofuran and cyclopentyl methyl ether for green solid-phase peptide synthesis.

2-MeTHF and CPME were evaluated as greener alternatives for the most employed solvents in peptide synthesis. The ability of these solvents to dissolve amino acid derivatives and a range of coupling reagents were evaluated as well as the swelling of polystyrene and polyethylene glycol resins. In addition, racemization and coupling efficiencies were also determined.

Hantzsch dihydropyridines: Privileged structures for the formation of well-defined gold nanostars.

Anisotropic and branched gold nanoparticles have great potential in optical, chemical and biomedical applications. However their syntheses involve multi-step protocols and the use of cytotoxic agents. Here, we report a novel one-step method for the preparation of gold nanostructures using only Hantzsch 1,4-dihydropyridines as mild reducing agents.

Peptide synthesis beyond DMF: THF and ACN as excellent and friendlier alternatives.

To date, DMF has been considered as the only solvent suitable for peptide synthesis. Here we demonstrate the capacity of THF and ACN, which are friendlier solvents than DMF, to yield the product in higher purity than DMF. Using various peptide models, both THF and ACN reduced racemization in solution-phase and solid-phase synthesis when compared with DMF.

Solid-phase peptide synthesis (SPPS), C-terminal vs. side-chain anchoring: a reality or a myth.

Here we review the strategies for the solid-phase synthesis of peptides starting from the side chain of the C-terminal amino acid. Furthermore, we provide experimental data to support that C-terminal and side-chain syntheses give similar results in terms of purity. However, the stability of the two bonds that anchor the peptide to the polymer may determine the overall yield and this should be considered for the large-scale production of peptides.

Neurotoxicity of prion peptides mimicking the central domain of the cellular prion protein.

The physiological functions of PrP(C) remain enigmatic, but the central domain, comprising highly conserved regions of the protein may play an important role. Indeed, a large number of studies indicate that synthetic peptides containing residues 106-126 (CR) located in the central domain (CD, 95-133) of PrP(C) are neurotoxic. The central domain comprises two chemically distinct subdomains, the charge cluster (CC, 95-110) and a hydrophobic region (HR, 112-133).

Synthesis and in vivo evaluation of the biodistribution of a 18F-labeled conjugate gold-nanoparticle-peptide with potential biomedical application.

Gold nanoparticles (AuNPs) have been extensively used in biological applications because of their biocompatibility, size, and ease of characterization, as well as an extensive knowledge of their surface chemistry. These features make AuNPs readily exploitable for biomedical applications, including drug delivery and novel diagnostic and therapeutic approaches. In a previous work, we studied ex vivo distribution of the conjugate C(AuNP)-LPFFD for its potential uses in the treatment of Alzheimer's disease.

Cell adhesion and focal contact formation on linear RGD molecular gradients: study of non-linear concentration dependence effects.

Unlabelled: Cell adhesion onto bioengineered surfaces is affected by a number of variables, including the former substrate derivatization process. In this investigation, we studied the correlation between cell adhesion and cell-adhesive ligand surface concentration and organization due to substrate modification. For this purpose, Arg-Gly-Asp (RGD) gradient surfaces were created on poly(methyl methacrylate) substrates by continuous hydrolysis and were then grafted with biotin-PEG-RGD molecules.

Solid-phase peptide synthesis using acetonitrile as a solvent in combination with PEG-based resins.

This manuscript shows that ACN can be an excellent choice for the coupling of hindered amino acids as illustrated by the coupling of Fmoc-amino acids on free amino acids anchored on a BAL synthesis. Furthermore, ACN can be a good alternative for solid-phase peptide synthesis in the absence of DMF (washings, removal of Fmoc, and coupling).

Convergent approaches for the synthesis of the antitumoral peptide, Kahalalide F. Study of orthogonal protecting groups.

Kahalalide compounds are peptides that are isolated from a Hawaiian herbivorous marine species of mollusc, Elysia rufescens, and its diet, the green alga Bryopsis sp. Kahalalide F and its synthetic analogues are the most promising compounds of the Kahalalide family because they show antitumoral activity. Linear solid-phase syntheses of Kahalalide F have been reported.