Co-liposomes comprising a lipidated multivalent RGD-peptide and a cationic gemini cholesterol induce selective gene transfection in alpha v beta 3 and alpha v beta 5 integrin receptor-rich cancer cells

The alpha v beta 3 and alpha v beta 5 integrins, transmembrane glycoprotein receptors, are over-expressed in numerous tumors and in endothelial cells that constitute tumor blood vessels. As this protein selectively binds to the Arg-Gly-Asp (RGD) sequence containing peptides, it is an attractive way to target tumors. Herein we have developed novel formulations for integrin mediated selective gene delivery. These formulations are composed of a novel palmitoylated tetrameric RGD containing scaffold (named RAFT-RGD), cationic gemini cholesterol (GL5) and a natural helper lipid 1,2-dioleoyl-L-alpha-glycero-3-phosphatidylethanolamine (DOPE). We have optimized a co-liposomal formulation to introduce the multivalent RGD-containing macromolecule in GL5: DOPE (GL5D) mixture to produce GL5D-RGD. We have unambiguously shown the selectivity of these formulations towards cancer cells that over express alpha v beta 3 and alpha v beta 5 integrins. Two reporter plasmids, pEGFP-C3 and PGL-3, were employed for the transfection experiments and it was shown that GL5D-RGD Liposomes increased exclusively the transfection in alpha v beta 3 and alpha v beta 5 overexpressing HeLa cells.

Multicomponent Assembly of Fluorescent-Tag Functionalized Ligands in Metal-Organic Frameworks for Sensing Explosives

Detection of trace amounts of explosive materials is significantly important for security concerns and pollution control. Four multicomponent metal organic frameworks (MOFs-12, 13, 23, and 123) have been synthesized by employing ligands embedded with fluorescent tags. The multicomponent assembly of the ligands was utilized to acquire a diverse electronic behavior of the MOFs and the fluorescent tags were strategically chosen to enhance the electron density in the MOFs. The phase purity of the MOFs was established by PXRD, NMR spectroscopy, and finally by singlecrystal XRD. Single-crystal structures of the MOFs-12 and 13 showed the formation of three-dimensional porous networks with the aromatic tags projecting inwardly into the pores. These electron-rich MOFs were utilized for detection of ex- plosive nitroaromatic compounds (NACs) through fluorescence quenching with high selectivity and sensitivity. The rate of fluorescence quenching for all the MOFs follows the order of electron deficiency of the NACs. We also showed the detection of picric acid (PA) by luminescent MOFs is not always reliable and can be misleading. This attracts our attention to explore these MOFs for sensing picryl chloride (PC), which is as explosive as picric acid and used widely to prepare more stable explosives like 2,4,6-trinitroaniline from PA. Moreover, the recyclability and sensitivity studies indicated that these MOFs can be reused several times with parts per billion (ppb) levels of sensitivity towards PC and 2,4,6-trinitrotoluene (TNT).

Hetero-tri-spin 2p-3d-4f] Chain Compounds Based on Nitronyl Nitroxide Lanthanide Metallo-Ligands: Synthesis, Structure, and Magnetic Properties

Employing nitronyl nitroxide lanthanide(III) complexes as metallo-ligands allowed the efficient and highly selective preparation of three series of unprecedented heterotri-spin (Cu Ln-radical) one-dimensional compounds. These 2p-3d-4f spin systems, namely Ln(3)Cu(hfac)II(NitPhOAII)41 (Ln(III)=Gd 1(Gd), Tb 1(Tb), Dy 1(Dy); NitPhOAII=2-(4'-allyloxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3- oxide), Ln(3)Cu(hfac)II(NitPhOPO4] (1-nrn=Gd 2Gd, Tb 2Tb, Dy 2(Dy), Ho 2HOf Yb 2yb; NitPhOPr= 2-(4'-propoxyphenyI)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide) and Ln3Cu(hfac)II(NitPhOB441 (LnIm=Gd 3Gd, Tb 3Tb, Dy 3(Dy); NitPhOBz=2-(4'-benzyloxy- phenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide) involve O-bound nitronyl nitroxide radicals as bridging ligands in chain structures with a Cu-Nit-Ln-Nit-Ln-Nit-Ln-Nit] repeating unit. The dc magnetic studies show that ferromagnetic metal radical interactions take place in these heterotri-spin chain complexes, these and the next-neighbor interactions have been quantified for the Gd derivatives. Complexes 1Tb and 2Tb exhibit frequency dependence of ac magnetic susceptibilities, indicating single-chain magnet behavior.

Simultaneous co-ordination of three cytosine ligands displaying different binding sites around the copper centres

We report the synthesis and structural characterization of a polymeric ternary copper-cytosine-phenanthroline complex, Cu-4(phen)(3)-(mu(3)-cyt)(2)(mu-OH)(cyt)(OH)Cl-3](n)center dot 16H(2)O, where three cytosine ligands with different binding sites have simultaneously complexed to the four copper metal centres. Interestingly, the complex exhibits two different coordination geometries around the metal centres.

Identifying functionally important cis-peptide containing segments in proteins and their utility in molecular function annotation

Cis-peptide embedded segments are rare in proteins but often highlight their important role in molecular function when they do occur. The high evolutionary conservation of these segments illustrates this observation almost universally, although no attempt has been made to systematically use this information for the purpose of function annotation. In the present study, we demonstrate how geometric clustering and level-specific Gene Ontology molecular-function terms (also known as annotations) can be used in a statistically significant manner to identify cis-embedded segments in a protein linked to its molecular function. The present study identifies novel cis-peptide fragments, which are subsequently used for fragment-based function annotation. Annotation recall benchmarks interpreted using the receiver-operator characteristic plot returned an area-under-curve >0.9, corroborating the utility of the annotation method. In addition, we identified cis-peptide fragments occurring in conjunction with functionally important trans-peptide fragments, providing additional insights into molecular function. We further illustrate the applicability of our method in function annotation where homology-based annotation transfer is not possible. The findings of the present study add to the repertoire of function annotation approaches and also facilitate engineering, design and allied studies around the cis-peptide neighborhood of proteins.

Directing peptide conformation with centrally positioned pre-organized dipeptide segments: studies of a 12-residue helix and beta-hairpin

Secondary structure formation in oligopeptides can be induced by short nucleating segments with a high propensity to form hydrogen bonded turn conformations. Type I/III turns facilitate helical folding while type II'/I' turns favour hairpin formation. This principle is experimentally verified by studies of two designed dodecapeptides, Boc-Val-Phe-Leu-Phe-Val-Aib-Aib-Val-Phe-Leu-Phe-Val-OMe 1 and Boc-Val-Phe-Leu-Phe-Val- (D) Pro- (L) Pro-Val-Phe-Leu-Phe-Val-OMe 2. The N- and C-terminal flanking pentapeptide sequences in both cases are identical. Peptide 1 adopts a largely alpha-helical conformation in crystals, with a small 3(10) helical segment at the N-terminus. The overall helical fold is maintained in methanol solution as evidenced by NMR studies. Peptide 2 adopts an antiparallel beta-hairpin conformation stabilized by 6 interstrand hydrogen bonds. Key nuclear Overhauser effects (NOEs) provide evidence for the antiparallel beta-hairpin structure. Aromatic proton chemical shifts provide a clear distinction between the conformation of peptides 1 (helical) and 2 (beta-hairpin). The proximity of facing aromatic residues positioned at non-hydrogen bonding positions in the hairpin results in extensively ring current shifted proton resonances in peptide 2.

Reduced Hornbill Abundance Associated with Low Seed Arrival and Altered Recruitment in a Hunted and Logged Tropical Forest

Logging and hunting are two key direct threats to the survival of wildlife in the tropics, and also disrupt important ecosystem processes. We investigated the impacts of these two factors on the different stages of the seed dispersal cycle, including abundance of plants and their dispersers and dispersal of seeds and recruitment, in a tropical forest in north-east India. We focused on hornbills, which are important seed dispersers in these forests, and their food tree species. We compared abundances of hornbill food tree species in a site with high logging and hunting pressures (heavily disturbed) with a site that had no logging and relatively low levels of hunting (less disturbed) to understand logging impacts on hornbill food tree abundance. We compared hornbill abundances across these two sites. We, then, compared the scatter-dispersed seed arrival of five large-seeded tree species and the recruitment of four of those species. Abundances of hornbill food trees that are preferentially targeted by logging were two times higher in the less disturbed site as compared to the heavily disturbed site while that of hornbills was 22 times higher. The arrival of scatter-dispersed seeds was seven times higher in the less disturbed site. Abundances of recruits of two tree species were significantly higher in the less disturbed site. For another species, abundances of younger recruits were significantly lower while that of older recruits were higher in the heavily disturbed site. Our findings suggest that logging reduces food plant abundance for an important frugivore-seed disperser group, while hunting diminishes disperser abundances, with an associated reduction in seed arrival and altered recruitment of animal-dispersed tree species in the disturbed site. Based on our results, we present a conceptual model depicting the relationships and pathways between vertebrate-dispersed trees, their dispersers, and the impacts of hunting and logging on these pathways.

The peptide NCbz-Val-Tyr-OMe and aromatic pi-pi interactions

The peptide N-benzyloxycarbonyl-L-valyl-L-tyrosine methyl ester or NCbz-Val-Tyr-OMe (where NCbz is N-benzyloxycarbonyl and OMe indicates the methyl ester), C23H28N2O6, has an extended backbone conformation. The aromatic rings of the Tyr residue and the NCbz group are involved in various attractive intra- and intermolecular aromatic - interactions which stabilize the conformation and packing in the crystal structure, in addition to NH...O and OH...O hydrogen bonds. The aromatic - interactions include parallel-displaced, perpendicular T-shaped, perpendicular L-shaped and inclined orientations.

Effects of hydrogen bonding on amide-proton chemical shift anisotropy in a proline-containing model peptide

Longitudinal relaxation due to cross-correlation between dipolar ((HN-1H alpha)-H-1) and amide-proton chemical shift anisotropy (H-1(N) CSA) has been measured in a model tripeptide Piv-(L)Pro-(L)Pro-(L)Phe-OMe. The peptide bond across diproline segment is known to undergo cis/trans isomerization and only in the cis form does the lone Phe amide-proton become involved in intramolecular hydrogen bonding. The strength of the cross correlated relaxation interference is found to be significantly different between cis and trans forms, and this difference is shown as an influence of intramolecular hydrogen bonding on the amide-proton CSA. (C) 2015 Elsevier B.V. All rights reserved.

Peculiar morphological transitions induced by nanoparticles in polymeric blends: retarded relaxation or altered interfacial tension?

Nanoparticles of different shapes can induce peculiar morphologies in binary polymer blends depending on their position. It is envisaged that the increased yield stress of the filled phase slows down the relaxation resulting in arresting the peculiar morphologies which otherwise is thermodynamically unfavourable due to the increased interfacial area. This essentially means that the highly irregular structures can be preserved even without altering the interfacial tension between the phases! On the other hand, in the case of interfacially adsorbed particles, the resulting solid-like interface can also preserve the irregular structures. These phenomenal transitions in filled blends are very different from the classical copolymer compatibilized polymer blends. Moreover, these irregular structures can further pave way in designing conducting polymer blends involving conducting nanoparticles and revisiting our understanding of the concept of double percolation!

The crystal structure of a lectin from Butea monosperma: Insight into its glycosylation and binding of ligands

Crystal structure of a lectin purified from Butea monosperma seeds was determined by Molecular Replacement method. Its primary structure was determined by Tandem Mass Spectroscopy and electron density maps from X-ray diffraction data. Its quaternary structure was tetrameric, formed of two monomers, alpha and beta, beta appearing as truncated alpha. The occurrence of two tetramers in the asymmetric unit of the crystal might be a consequence of asymmetric contacts due to difference in glycosylation and variable loops structures, to form an `octamer-structure'. The crystal structure showed binding pockets for gamma Abu, having a proposed role in plant defense, at the interface of canonical dimer-partners. Hemagglutination studies, enzyme kinetics, isothermal titration calorimetry and molecular dynamics showed that the lectin is specific to N-acetyl D-galactosamine, galactose and lactose in decreasing order, and alpha-amylase inhibitor. (C) 2014 Elsevier B.V. All rights reserved.

New dimeric carbazole-benzimidazole mixed ligands for the stabilization of human telomeric G-quadruplex DNA and as telomerase inhibitors. A remarkable influence of the spacer

for selectively targeting cancer cells. Herein, we report the design and evolution of a new kind of carbazole-based benzimidazole dimers for their efficient telomerase inhibition activity. Spectroscopic titrations reveal the ligands high affinity toward the G4 DNA with significantly higher selectivity over duplex-DNA. The electrophoretic mobility shift assay shows that the ligands efficiently promote the formation of 04 DNA even at a lower concentration of the stabilizing K+ ions. The TRAP-LIG assay demonstrates the ligand's potential telomerase inhibition activity and also establishes that the activity proceeds via G4 DNA stabilization. An efficient nuclear internalization of the ligands in several common cancer cells (HeLa, HT1080, and A549) also enabled differentiation between normal HFF cells in co-cultures of cancer and normal ones. The ligands induce significant apoptotic response and antiproliferative activity toward cancer cells selectively when compared to the normal cells.

A sleep-inducing peptide from the venom of the Indian cone snail Conus araneosus

The marine snail Conus araneosus has unusual significance due to its confined distribution to coastal regions of southeast India and Sri Lanka. Due to its relative scarceness, this species has been poorly studied. In this work, we characterized the venom of C. araneosus to identify new venom peptides. We identified 14 novel compounds. We determined amino acid sequences from chemically-modified and unmodified crude venom using liquid chromatography-electrospray ionization mass spectrometry and matrix assisted laser desorption ionization time-of-flight mass spectrometry. Ten sequences showed six Cys residues arranged in a pattern that is most commonly associated with the M-superfamily of conotoxins. Four other sequences had four Cys residues in a pattern that is most commonly associated with the T-superfamily of conotoxins. The post-translationally modified residue (pyroglutamate) was determined at the N-terminus of two sequences, ar3h and ar3i respectively. In addition, two sequences, ar3g and ar3h were C-terminally amidated. At a dose of 2 nmol, peptide ar3j elicited sleep when injected intraperitoneally into mice. To our knowledge, this is the first report of a peptide from a molluscivorous cone snail with sleep-inducing effects in mice. The novel peptides characterized herein extend the repertoire of unique peptides derived from cone snails and may add value to the therapeutic promise of conotoxins. (C) 2015 Elsevier Ltd. All rights reserved.

Zinc acetylacetonate hydrate adducted with nitrogen donor ligands: Synthesis, spectroscopic characterization, and thermal analysis

We report synthesis, spectroscopic characterization, and thermal analysis of zinc acetylacetonate complex adducted by nitrogen donor ligands, such as pyridine, bipyridine, and phenanthroline. The pyridine adducted complex crystallizes to monoclinic crystal structure, whereas other two adducted complexes have orthorhombic structure. Addition of nitrogen donor ligands enhances the thermal property of these complexes as that with parent metal-organic complex. Zinc acetylacetonate adducted with pyridine shows much higher volatility (106 degrees C), decomposition temperature (202 degrees C) as that with zinc acetylacetonate (136 degrees C, 220 degrees C), and other adducted complexes. All the adducted complexes are thermally stable, highly volatile and are considered to be suitable precursors for metal organic chemical vapor deposition. The formation of these complexes is confirmed by powder X-ray diffraction, Fourier transform infrared spectroscopy, mass spectroscopy, and elemental analysis. The complexes are widely used as starting precursor materials for the synthesis of ZnO nanostructures by microwave irradiation assisted coating process. (c) 2015 Elsevier B.V. All rights reserved.