Selective Recognition of Conformation-Specific Arylamine-DNA Adduct in Frameshift Model by [Ru(phen)2(dppz)]2.

Arylamine modification of guanine base at the G3 position in the NarI sequence (-G1G2CG3CC-) causes a frameshift mutation. Polymerase and 19F NMR studies have shown that the next flanking base at the 3' position to the G3 adduct modulates the mutational outcome because of its different conformations. Here, we have studied the interaction of the 16-mer NarI sequence (5'-CTCTCG1G2CG3CXATCAC-3') (G3 = N-acetyl-2-aminofluorene (AAF)-dG and X is either C or T) with [Ru(phen)2(dppz)]2+ (phen = 1,10-phenanthroline and dppz = dipyrido[3,2-a:2',3'-c]phenazine). Interaction studies between isomers of Ru(II) and two oligonucleotide models, viz., (a) full duplex, and (b) slipped mutagenic intermediate (SMI), have been carried out. Luminescence studies reveal that the sensitivity of Ru(II) with an adduct increases 2- to 3-fold compared to that of control in full duplex. In SMI, the sensitivity of Ru(II) varies with the next flanking base and in the order of -GAAFCC > -GAAFCT. Microscale thermophoretic data reveal that in full duplex Λ-Ru binds to -GAAFCT- by 13- and 4-fold stronger than its control and -GAAFCC-, respectively. In SMI, Δ-Ru binds to -GAAFCC- (41% stacked (S) conformer) by 3-fold while -GAAFCT- (86% major groove (B) conformer) weakens the binding of Λ-Ru by 250-fold compared to the control. The results presented here reveal that the binding of Ru(II) not only depends on conformations of the AAF-dG adduct but also is isomer-centric and might be helpful in determining the conformational heterogeneity of other covalent aryl/heterocyclic amine-DNA adducts.

Photocrosslinking of collagen using Ru(II)-polypyridyl complex functionalized gold nanoparticles.

Collagen, an extracellular matrix protein, has been used for diverse biological applications due to its clinically safe in nature and for the development of various biomedical devices. As the ECM protein is prone to degradation process, it is necessary to stabilize the collagen. In the present study, we have carried out the stabilization of collagen using newly synthesized gold nanoparticles conjugated with Ru(II) complexes (NCs) possessing different ligand environment. From the DLS measurements, the size of the nanoparticles varies from 20 ±â€¯6 nm. Fibrillation assay studies show that the NCs in the presence of photo-irradiation delays the fibrillation process significantly, while in the presence of persulfate, the acceleration in fibrillation process occurs. Circular dichroic and infra-red spectroscopic studies reveal that no alteration in triple helical structure observed for the photo-irradiated samples. SDS-PAGE analysis data reveal that the NCs facilitate the collagen crosslinks and hinders the enzymatic digestion, while neither Au-NPs nor Ru(II) complexes alone did not impart any stability to the collagen. The results from this study help us to understand the photochemical reaction of nanoparticle conjugate on collagen crosslinking and might be helpful in developing new photocatalyst for corneal application.

Dihydroactinidiolide, a natural product against Aß25-35 induced toxicity in Neuro2a cells: Synthesis, in silico and in vitro studies.

Synthesis of natural products has speeded up drug discovery process by minimizing the time for their purification from natural source. Several diseases like Alzheimer's disease (AD) demand exploring multi targeted drug candidates, and for the first time we report the multi AD target inhibitory potential of synthesized dihydroactinidiolide (DA). Though the activity of DA in several solvent extracts have been proved to possess free radical scavenging, anti bacterial and anti cancer activities, its neuroprotective efficacy has not been evidenced yet. Hence DA was successfully synthesized from ß-ionone using facile two-step oxidation method. It showed potent acetylcholinesterase (AChE) inhibition with half maximal inhibitory concentration (IC50) 34.03 nM, which was further supported by molecular docking results showing strong H bonding with some of the active site residues such as GLY117, GLY119 and SER200 of AChE. Further it displayed DPPH and (.NO) scavenging activity with IC50 value 50 nM and metal chelating activity with IC50 >270 nM. Besides, it significantly prevented amyloid ß25-35 self-aggregation and promoted its disaggregation at 270 nM. It did not show cytotoxic effect towards Neuro2a (N2a) cells up to 24 h at 50 and 270 nM while it significantly increased viability of amyloid ß25-35 treated N2a cells through ROS generation at both the concentrations. Cytotoxicity profile of DA against human PBMC was quite impressive. Hemolysis studies also revealed very low hemolysis i.e. minimum 2.35 to maximum 5.61%. It also had suitable ADME properties which proved its druglikeness. The current findings demand for further in vitro and in vivo studies to develop DA as a multi target lead against AD.

Elastic compliance of fibrillar assemblies in type I collagen.

Fibrillary assemblies of Type I collagen find important applications in tissue engineering and as matrices for biophysical studies. The mechanical and structural properties of these structures are governed by factors such as protein concentration, temperature, pH and ionic strength. This study reports on an impedance based analysis of the elastic compliance of fibrillary assemblies of Type I collagen using quartz crystal microbalance with dissipation (QCM-D) at a fundamental frequency of 5 MHz and overtones (n = 3,5,7,9,11). Here, In situ partial fibrillation of the adsorbing collagen followed by its fibrillary assemblies on hydrophilic gold coated quartz surface have been crosslinked using Gallic acid (GA), Chromium (III) gallate (Cr-GA), Catechin (Cat), Tetrakis(hydroxymethyl)phosphonium sulfate (THPS) and Oxazolidine (Ox). This approach allows direct comparison of how viscoelastic properties track the structural evolution of the fiber and network length scales. The collagen crosslinking shows significant positive impact on the protein's mechanical behaviour and on the type of crosslinking agents used. The elastic modulus increases as collagen