Detection of amyloid-beta by Fmoc-KLVFF self-assembled fluorescent nanoparticles for Alzheimer's disease diagnosis

The abnormal aggregation of amyloid-beta(Aβ) has been widely believed to play an important role in the pathogenesis of Alz heimer's disease(AD),which is also recognized as one of the main biomarkers for AD diagnosis.The peptide sequence Lys-Leu-Val-Phe-Phe(KLVFF) is considered as the main driver of the fibrillation of Aβ,which also can be utilized to target Aβ and inhibit its aggregation.In this study,KLVFF and Fmoc-KLVFF fluorescent nanoparticles were self-assembled through zinc coordination and π-πstacking.The recognition of Aβ aggregates including oligomers and fibrils by fluorescent nanoparticles can be realized through aromatic,hydrophobic,and hydrogen-bond interactions.The fluorescent nanoprobes can distinguish Aβ aggregation formats and detect Aβ at the limit of 1 pg/mL(S/N=3).Hence,the detection of Aβ aggregates by fluorescent peptide nanoparticles has great potential for AD diagnosis and progression prediction.     

The first two structurally characterized energetic catalysts derived from dinitropyridone

Two energetic catalysts, 3,5-dinitro-2-pyridonate of lead (II) (Pb(2DNPO)₂, 1) and 3,5-dinitro-4-pyridone-N-hydroxylate tetrahydrate of copper (II) (Cu(4DNPOH)₂(H₂O)₄, 2) were characterized by elemental analysis, FT-IR, TG-DSC and structurally characterized by X-ray single-crystal diffraction analysis. X-ray powder diffraction analysis of complex 1 confirmed the phase homogeneity of the polycrystalline sample. Crystal data for 1: monoclinic, space group P 21/n, a = 8.5253(9), b = 9.2938(10), c = 19.654(2) Å, β = 102.289(2)°, V = 1521.6(3) ų, Z = 4; 2: monoclinic, space group P 21/n , a = 8.3705(10), b = 9.9307(12), c = 10.5771(12) Å, β = 98.021(2)°, V = 870.62(18) ų, Z = 2. The complex 1 is a one-dimensional coordination polymer with each Pb(II) atom being six-coordinated, forming a heavily distorted octahedral geometry, by two nitrogen and four oxygen donors. Each ligand links the Pb(II) ions in a chelating bridging mode using nitrogen and oxygen atoms of its pyridonate part. The complex 2 is a copper (II) complex with a compressed octahedral geometry. The Cu(II) atom locates on the equatorial positions defined by oxygen atoms of four water molecules. Its axial positions are filled with two oxygen donors of the pyridine-N-hydroxylate moieties of two ligands. The abundant hydrogen bonds link the molecules into one-dimensional chains. Both the complexes represent the first two examples of the energetic catalysts containing dinitropyridine derivatives characterized crystallographically     

Formation of (b<Subscript><Emphasis Type="Italic">n</Emphasis>−1</Subscript> + H<Subscript>2</Subscript>O) ions by collisional activation of maldi-formed peptide [M + H]<Superscript>+</Superscript> ions in a QqTOF mass spectrometer

Collisional activation of [M + H](+) parent ions from peptides of n amino acid residues may yield a rearrangement that involves loss of the C-terminal amino acid residue to produce (b(n-1) + H(2)O) daughters. We have studied this reaction by a retrospective examination of the m/z spectra of two collections of data. The first set comprised 398 peptides from coat protein digests of a number of plant viruses by various enzymes, where conditions in the tryptic digests were chosen so as to produce many missed cleavages. In this case, a large effect was observed-323 (b(n-1) + H(2)O) daughter ions (approximately 81%), including 185 (approximately 46%) "strong" decays with ratios (b(n-1) + H(2)O)/(b(n-1)) > 1. The second set comprised 1200 peptides, all from tryptic digests, which were carried out under more stringent conditions, resulting in relatively few missed cleavages. Even here, 190 (b(n-1) + H(2)O) ions (approximately 16%) were observed, including 87 (> 7%) "strong" decays, so the effect is still appreciable. The results suggest that the tendency for (b(n-1) + H(2)O) ion formation is promoted by the protonated side chain of a non-C-terminal basic amino acid residue, in the order arginine > lysine > or = histidine, and that its (non-C-terminal) position is not critical. The results can be interpreted by a mechanism in which hydrogen bonding between the protonated side chain and the (n - 1) carbonyl oxygen facilitates loss of the C-terminal amino acid residue to give a product ion having a carboxyl group at the new C-terminus.     

1H and 13C NMR assignments for two oxaphenalenones bacillosporin C and D from the mangrove endophytic fungus SBE-14

The complete (1)H and (13)C NMR assignments are reported for the novel natural product Bacillosporin D together with the known compound Bacillosporin C. These compounds containing seven rings were isolated from the mangrove endophytic fungus SBE-14 from the South China Sea. 1D and 2D NMR experiments, including COSY, HMQC and HMBC were used to the determination of the structures and NMR assignments. It is proposed that 1 was biogenetically produced by transforming 2. Transforming a lactone to an anhydride is unusual in nature.     

Bead-based immunoassays using a micro-chip flow cytometer

A microfabricated flow cytometer has been developed for the analysis of micron-sized polymer beads onto which fluorescently labelled proteins have been immobilised. Fluorescence measurements were made on the beads as they flowed through the chip. Binding of antibodies to surface-immobilised antigens was quantitatively assayed using the device. Particles were focused through a detection zone in the centre of the flow channel using negative dielectrophoresis. Impedance measurements of the particles (at 703 kHz) were used to determine particle size and to trigger capture of the fluorescence signal. Antibody binding was measured by fluorescence at single and dual excitation wavelengths (532 nm and 633 nm). Fluorescence compensation techniques were implemented to correct for spectral overspill between optical detection channels. The data from the microfabricated flow cytometer was shown to be comparable to that of a commercial flow cytometer (BD-FACSAria).     

Concise formal synthesis of (+)-neopeltolide

A concise formal synthesis of (+)-neopeltolide (1) has been accomplished. The synthesis demonstrated high atom efficiency employing only one step of functional group protection. Key steps involved iridium-catalyzed double asymmetric carbonyl allylation, palladium-catalyzed intramolecular alkoxycarbonylation, ruthenium-catalyzed olefin isomerization, and ring-closing metathesis.     

N-heterocyclic carbene-catalyzed cascade epoxide-opening and lactonization reaction for the synthesis of dihydropyrone derivatives

N-Heterocyclic carbene was employed as an efficient organic catalyst to catalyze a cascade epoxide-opening and lactonization reaction. This organocatalytic process could transform various readily accessible γ-epoxy-α,β-enals into dihydropyrone derivatives in good to excellent yields.     

Total synthesis of cyanolide A

The total synthesis of cyanolide A has been achieved in 14 steps from commercially available (S)-2-ethyloxirane, exploiting the palladium-catalyzed intramolecular alkoxycarbonylation as the key step to construct the tetrasubstituted cis-tetrahydropyran ring with high stereoselectivity.     

PtI2-catalyzed tandem 3,3-rearrangement/Nazarov reaction of arylpropargylic esters: synthesis of indanone derivatives

An efficient PtI(2)-catalyzed tandem reaction of arylpropargylic esters, involving 3,3-rearrangement and Nazarov reaction, has been developed to produce 3-substituted and 3,3-disubstituted indanone derivatives. This approach provided a pathway to the synthesis of indanone skeletons in natural products.     

Concise total synthesis of (±)-dasyscyphin D

The first and efficient total synthesis of (±)-dasyscyphin D was achieved in 9 steps with 22.6% overall yield. The key steps involved a PtCl(2)-catalyzed pentannulation reaction and acid-catalyzed double Robinson annulations.