Boosting the Synthesis of Pharmaceutically Active Abietane Diterpenes in Hairy Roots by Engineering the and Genes.

Abietane diterpenoids (ADs), synthesized in the roots of different species, such as aethiopinone, 1-oxoaethiopinone, salvipisone, and ferruginol, have a variety of known biological activities. We have shown that aethiopinone has promising cytotoxic activity against several human tumor cell lines, including the breast adenocarcinoma MCF7, HeLa, epithelial carcinoma, prostate adenocarcinoma PC3, and human melanoma A375. The low content of these compounds in natural sources, and the limited possibility to synthesize them chemically at low cost, prompted us to optimize the production of abietane diterpenoids by targeting genes of the methylerythritol phosphate (MEP) pathway, from which they are derived.

Coactivation of MEP-biosynthetic genes and accumulation of abietane diterpenes in Salvia sclarea by heterologous expression of WRKY and MYC2 transcription factors.

Plant abietane diterpenoids (e.g. aethiopinone, 1- oxoaethiopinone, salvipisone and ferruginol), synthesized in the roots of several Salvia spp, have antibacterial, antifungal, sedative and anti-proliferative properties.

Discovery and synthesis of the first selective BAG domain modulator of BAG3 as an attractive candidate for the development of a new class of chemotherapeutics.

BAG3 protein has emerged as a key regulator of important cellular processes and its expression is increased in some tumor types; however, despite its potential value for future chemotherapeutics, no selective BAG3 modulators have been yet reported. Here we report the 2,4-thiazolidinedione derivative 28 as the first BAG3 protein modulator.

Cyclic Peptoids as Mycotoxin Mimics: An Exploration of Their Structural and Biological Properties.

Cyclic peptoids have recently emerged as important examples of peptidomimetics for their interesting complexing properties and innate ability to permeate biological barriers. In the present contribution, experimental and theoretical data evidence the intricate conformational and stereochemical properties of five novel hexameric peptoids decorated with N-isopropyl, N-isobutyl, and N-benzyl substituents. Complexation studies by NMR, in the presence of sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (NaTFPB), theoretical calculations, and single-crystal X-ray analyses indicate that the conformationally stable host/guest metal adducts display architectural ordering comparable to that of the enniatins and beauvericin mycotoxins.

Cytoskeletal proteins associate with components of the ribosomal maturation and translation apparatus in Xenopus stage I oocytes.

Actin-based cytoskeleton (CSK) and microtubules may bind to RNAs and related molecules implicated in translation. However, many questions remain to be answered regarding the role of cytoskeletal components in supporting the proteins involved in steps in the maturation and translation processes. Here, we performed co-immunoprecipitation and immunofluorescence to examine the association between spectrins, keratins and tubulin and proteins involved in 60S ribosomal maturation and translation in Xenopus stage I oocytes, including ribosomal rpl10, eukaryotic initiation factor 6 (Eif6), thesaurins A/B, homologs of the eEF1α elongation factor, and P0, the ribosomal stalk protein.

Identification of the plant compound geraniin as a novel Hsp90 inhibitor.

Besides its function in normal cellular growth, the molecular chaperone heat shock protein 90 (Hsp90) binds to a large number of client proteins required for promoting cancer cell growth and/or survival. In an effort to discover new small molecules able to inhibit the Hsp90 ATPase and chaperoning activities, we screened, by a surface plasmon resonance assay, a small library including different plant polyphenols. The ellagitannin geraniin, was identified as the most promising molecule, showing a binding affinity to Hsp90α similar to that of 17-(allylamino)-17-demethoxygeldanamycin (17AGG).

Expression of p27BBP/eIF6 is highly modulated during Xenopus laevis embryogenesis.

Protein p27BBP/eIF6 is necessary for ribosomal function of all cells. Previous data showed that from mammals to yeast p27BBP/eIF6 is involved in the biogenesis of ribosomal subunit 60S and its association with the 60S prevents premature 80S formation regulated by PKC signaling, indicating that phosphorylation of p27BBP/eIF6 is needed for translation to occur. While in vitro p27BBP/eIF6 is constitutively expressed, and it has a high level of expression in cycling cells, in vivo its expression varies according to tissues and appears regulated by factors up to now unknown.

Sequencing and characterization of the Xenopus laevis ribosomal protein L34 cDNA.

In this paper, a cDNA homologous to the mammalian ribosomal protein (r-protein) L34 was isolated from a Xenopus laevis oocytes library and named XL34. It encodes a protein of 116 residues with an Mr of 13.2 kDa and a highly basic sequence.