Integrin alpha9 emerges as a key therapeutic target to reduce metastasis in rhabdomyosarcoma and neuroblastoma.

The majority of current cancer therapies are aimed at reducing tumour growth, but there is lack of viable pharmacological options to reduce the formation of metastasis. This is a paradox, since more than 90% of cancer deaths are attributable to metastatic progression. Integrin alpha9 (ITGA9) has been previously described as playing an essential role in metastasis; however, little is known about the mechanism that links this protein to this process, being one of the less studied integrins.

Conformational ensemble of the TNF-derived peptide solnatide in solution.

Tumor necrosis factor (TNF) is a homotrimer that has two spatially distinct binding regions, three lectin-like domains (LLD) at the TIP of the protein and three basolaterally located receptor-binding sites, the latter of which are responsible for the inflammatory and cell death-inducing properties of the cytokine. Solnatide (a.k.

Structure-based design of a Cortistatin analogue with immunomodulatory activity in models of inflammatory bowel disease.

Ulcerative colitis and Crohn's disease are forms of inflammatory bowel disease whose incidence and prevalence are increasing worldwide. These diseases lead to chronic inflammation of the gastrointestinal tract as a result of an abnormal response of the immune system. Recent studies positioned Cortistatin, which shows low stability in plasma, as a candidate for IBD treatment.

Topical administration of somatostatin prevents retinal neurodegeneration in experimental diabetes.

Retinal neurodegeneration is an early event in the pathogenesis of diabetic retinopathy (DR). Somatostatin (SST) is an endogenous neuroprotective peptide that is downregulated in the diabetic eye. The aim of the study was to test the usefulness of topical administration of SST in preventing retinal neurodegeneration.

Acridine and quindoline oligomers linked through a 4-aminoproline backbone prefer G-quadruplex structures.

Background: DNA-intercalating drugs are planar molecules with several fused aromatic rings that form stacks between DNA base pairs, reducing the opening and unwinding of the double helix. Recently, interest on intercalating agents has moved in the search for new ligands to G-quadruplex structures.

Methods: The DNA binding properties of 4-aminoproline oligomers functionalized with one, two or three units of acridine and/or quindoline have been analyzed by competitive dialysis.

Lamellarin D bioconjugates II: Synthesis and cellular internalization of dendrimer and nuclear location signal derivatives.

The design and synthesis of Lamellarin D conjugates with a nuclear localization signal peptide and a poly(ethylene glycol)-based dendrimer are described. Conjugates 1-4 were obtained in 8-84% overall yields from the corresponding protected Lamellarin D. Conjugates 1 and 4 are 1.

Cell-penetrating proline-rich peptidomimetics.

Cell-penetrating peptides (CPPs) offer potential as delivery agents for the cellular administration of drugs. However, the pharmacological utility of CPPs that are derived from natural amino acids is limited by their rapid metabolic degradation, low membrane permeability, and toxicity. Various peptidomimetics able to overcome these problems have been described, including peptides formed by D-amino acids and beta-peptides.

Solid-phase combinatorial synthesis of a lysyl-tRNA synthetase (LysRS) inhibitory library.

The solid-phase combinatorial synthesis of a new library with potential inhibitory activity against the cytoplasmic lysyl-tRNA synthetase (LysRS) isoform of Trypanosoma brucei is described. The library has been specifically designed to mimic the lysyl adenylate complex. The design was carried out by dividing the complex into four modular parts.

Solid-phase synthesis of oligomers carrying several chromophore units linked by phosphodiester backbones.

A method for the preparation of oligomers by linking chromophore units is described. Specifically, the synthesis of chromophore units having a protected-hydroxyl group and a phosphoramidite function is described, along with a method to link several units using solid-phase phosphite-triester protocols.

Design, synthesis and antiproliferative properties of oligomers with chromophore units linked by amide backbones.

The preparation of oligomers made up of several chromophore units as compounds with potential fluorescent and antiproliferative properties is described. Specifically, chromophore units with protected-amino groups and one carboxylic group are described, together with methods to assemble these units using peptide chemistry. Some of these compounds have antiproliferative activity.

Solid-phase synthesis of sulfamate peptidomimetics.

A synthetic method for the preparation of sulfamate peptidomimetics is described. The methodology allows sulfamoylation in the solid phase using sulfamoyl chloride in DMA, followed by the acylation of the corresponding sulfamoylated product. Following this approach, several derivatives have been prepared starting from distinct alcohol sources, including alpha-, beta-, and gamma-hydroxyacids and phenols.

Cell-penetrating cis-gamma-amino-l-proline-derived peptides.

The synthesis of cis-gamma-amino-l-proline oligomers functionalized at the proline alpha-amine with several groups that mimic the side chains of natural amino acids, including alanine, leucine, and phenylalanine, is herein described. These gamma-peptides enter into different cell lines (COS-1 and HeLa) via an endocytic mechanism. The ability of these compounds to be taken up into cells was studied at 37 degrees C and 4 degrees C by plate fluorimetry, flow cytometry, and confocal microscopy.

A new class of foldamers based on cis-gamma-amino-L-proline.

A synthetic method for the preparation of conformationally constrained gamma-peptides derived from gamma-amino-L-proline is described. The methodology allows the independent buildup of the peptide backbone and the introduction of sequential variations by reactions with the alpha-amino group of gamma-aminoproline. Both alkyl- and acyl-substituted gamma-peptides have been prepared and studied by CD and NMR.