Novel Insights for Inhibiting Mutant Heterodimer IDH1 in Cancer: An In-Silico Approach.

Background: Isocitrate dehydrogenase 1 (IDH1) is a dimeric enzyme responsible for supplying the cell's nicotinamide adenine dinucleotide phosphate (NADPH) reserves via dehydrogenation of isocitrate (ICT) and reduction of NADP+. Mutations in position R132 trigger cancer by enabling IDH1 to produce D-2-hydroxyglutarate (2-HG) and reduce inhibition by ICT. Mutant IDH1 can be found as a homodimer or a heterodimer.

Molecular determinants for cyclo-oligosaccharide-based nanoparticle-mediated effective siRNA transfection.

Aim: To study the structural requirements that a cyclooligosaccharide-based nanoparticle must fulfill to be an efficient siRNA transfection vector.

Materials & Methods: siRNA protection from degradation by RNAses, transfection efficiency and the thermodynamic parameters of the nanoparticle/siRNA interactions were studied on pairs of amphiphilic molecules using biochemical techniques and molecular dynamics.

Results: The lower the siRNA solvent accessible surface area in the presence of the nanoparticle, higher the protection from RNAse-mediated degradation in the corresponding nanocomplex; a moderate nanoparticle/siRNA binding energy value further facilitates reversible complexation and binding to the target cellular mRNA.

The complex of PAMAM-OH dendrimer with Angiotensin (1-7) prevented the disuse-induced skeletal muscle atrophy in mice.

Angiotensin (1-7) (Ang-(1-7)) is a bioactive heptapeptide with a short half-life and has beneficial effects in several tissues - among them, skeletal muscle - by preventing muscle atrophy. Dendrimers are promising vehicles for the protection and transport of numerous bioactive molecules. This work explored the use of a neutral, non-cytotoxic hydroxyl-terminated poly(amidoamine) (PAMAM-OH) dendrimer as an Ang-(1-7) carrier.

Multiscale Molecular Simulations Applied to Nucleic Acid-Dendrimer Interactions Studies.

Unlabelled: Dendrimers are monodisperse, regular, three-dimensional and small-scale macromolecules that can be used to release substances such as drugs, markers, and genetic material into the cells. Among these substances, nucleic acids such as plasmid DNA, antisense oligonucleotides (asODN), and small-interfering RNA (siRNA) are widely used as therapeutic macromolecules for the treatment and prevention of diverse diseases. Several studies were focused on the modification of dendrimers aiming to improve their affinity for nucleic acids and their ability to release nucleic acids inside the cells.

Effect of Several HIV Antigens Simultaneously Loaded with G2-NN16 Carbosilane Dendrimer in the Cell Uptake and Functionality of Human Dendritic Cells.

Dendrimers are highly branched, star-shaped, and nanosized polymers that have been proposed as new carriers for specific HIV-1 peptides. Dendritic cells (DCs) are the most-potent antigen-presenting cells that play a major role in the development of cell-mediated immunotherapy due to the generation and regulation of adaptive immune responses against HIV-1. This article reports on the associated behavior of two or three HIV-derived peptides simultaneously (p24/gp160 or p24/gp160/NEF) with cationic carbosilane dendrimer G2-NN16.

Self-Assembly of Amphiphilic Dendrimers: The Role of Generation and Alkyl Chain Length in siRNA Interaction.

An ideal nucleic-acid transfection system should combine the physical and chemical characteristics of cationic lipids and linear polymers to decrease cytotoxicity and uptake limitations. Previous research described new types of carriers termed amphiphilic dendrimers (ADs), which are based on polyamidoamine dendrimers (PAMAM). These ADs display the cell membrane affinity advantage of lipids and preserve the high affinity for DNA possessed by cationic dendrimers.

Biomimetics: From Bioinformatics to Rational Design of Dendrimers as Gene Carriers.

Biomimetics, or the use of principles of Nature for developing new materials, is a paradigm that could help Nanomedicine tremendously. One of the current challenges in Nanomedicine is the rational design of new efficient and safer gene carriers. Poly(amidoamine) (PAMAM) dendrimers are a well-known class of nanoparticles, extensively used as non-viral nucleic acid carriers, due to their positively charged end-groups.

pH-dependent nano-capturing of tartaric acid using dendrimers.

The ability of dendrimers to bind to various target molecules through non-covalent interactions was used to capture water soluble organic reagents, such as tartaric acid (TA), from different matrices, i.e. aqueous solutions and wine samples.

Penicillium purpurogenum produces two GH family 43 enzymes with β-xylosidase activity, one monofunctional and the other bifunctional: Biochemical and structural analyses explain the difference.

β-Xylosidases participate in xylan biodegradation, liberating xylose from the non-reducing end of xylooligosaccharides. The fungus Penicillium purpurogenum secretes two enzymes with β-D-xylosidase activity belonging to family 43 of the glycosyl hydrolases. One of these enzymes, arabinofuranosidase 3 (ABF3), is a bifunctional α-L-arabinofuranosidase/xylobiohydrolase active on p-nitrophenyl-α-L-arabinofuranoside (pNPAra) and p-nitrophenyl-β-D-xylopyranoside (pNPXyl) with a KM of 0.

Supramolecular complexes of quantum dots and a polyamidoamine (PAMAM)-folate derivative for molecular imaging of cancer cells.

Polyamidoamine (PAMAM) dendrimers and water-soluble 3-mercaptopropionic acid (MPA)-capped CdSe quantum dots (QDs) were combined to produce a new gel containing supramolecular complexes of QDs/PAMAM dendrimers. The formation of the QDs/PAMAM supramolecular complexes was confirmed by high resolution electron microscopy and Fourier transform infrared (FTIR) analyses. Molecular dynamics simulations corroborated the structure of the new QDs/PAMAM-based supramolecular compound.

Distributed structures underlie gating differences between the kin channel KAT1 and the Kout channel SKOR.

The family of voltage-gated (Shaker-like) potassium channels in plants includes both inward-rectifying (K(in)) channels that allow plant cells to accumulate K(+) and outward-rectifying (K(out)) channels that mediate K(+) efflux. Despite their close structural similarities, K(in) and K(out) channels differ in their gating sensitivity towards voltage and the extracellular K(+) concentration. We have carried out a systematic program of domain swapping between the K(out) channel SKOR and the K(in) channel KAT1 to examine the impacts on gating of the pore regions, the S4, S5, and the S6 helices.

Distinct roles of the last transmembrane domain in controlling Arabidopsis K+ channel activity.

The family of voltage-gated potassium channels in plants presumably evolved from a common ancestor and includes both inward-rectifying (K(in)) channels that allow plant cells to accumulate K(+) and outward-rectifying (K(out)) channels that mediate K(+) efflux. Despite their close structural similarities, the activity of K(in) channels is largely independent of K(+) and depends only on the transmembrane voltage, whereas that of K(out) channels responds to the membrane voltage and the prevailing extracellular K(+) concentration. Gating of potassium channels is achieved by structural rearrangements within the last transmembrane domain (S6).