Chiral alpha-aminoxy acid/achiral cyclopropane alpha-aminoxy acid unit as a building block for constructing the alpha N-O helix.

The monomer 1 derived from achiral 1-(aminoxy)cyclopropanecarboxylic acid (OAcc) and oligopeptides 2-9 consisting of a chiral alpha-aminoxy acid and an achiral alpha-aminoxy acid such as OAcc were synthesized and their structures characterized. The eight-membered-ring intramolecular hydrogen bond, namely the alpha N-O turn, was formed between adjacent residues independent of their chirality. However, the helix formation was sequence-dependent. Dipeptide 2 bearing chiral alpha-aminoxy acid (d-OAA) at the N-terminus and achiral OAcc at the C-terminus preferentially adopted a right-handed 1.8(8) helical structure, but dipeptide 3 (OAcc-d-OAA) did not. Theoretical calculation results, in good agreement with experimental ones, revealed that the biased handedness of alpha N-O turn found in OAcc residue depends on its preceding chiral residue. It was then found that the helical conformation was destroyed in the case of oligopeptides 6 and 7 [OAA-(OAcc)(n), n = 2, 3]. The crystal structure of tripeptide 8 ((i)PrCO-d-OVal-OAcc-d-OVal-NH(i)Bu) further disclosed the helical structure formed by three consecutive homochiral alpha N-O turns. This study has uncovered achiral aminoxy acid residues such as the OAcc unit as a useful building block to be incorporated into chiral aminoxy peptides to mimic chiral helix structure.

[Study on the property of CBD-CdS thin films].

CdS thin films were prepared by chemical bath deposition (CBD) at 90 'C. The influence of annealing and CdCl2 treatment on CBD-CdS thin film was studied. XRD and SEM were used to study the crystal structure and surface morphology ofthe films. The untreated CBD-CdS films had poor crystallinity; the CdS thin film made with annealing treatment had cubic crystallinity but small grain size. After the CdCl2 treatment, these films recrystallized to the hexagonal phase, resulting in a better crystallinity, and smooth surface morphology. Optical properties were studied by absorption spectrum. The energy gap of the films was found to decrease by annealing, and the CBD-CdS made with CdCl2 treatment had a lower density of planar defects. In conclusion, the CdCl2 treatment can improve the properties of the CdS thin films.

Dual-tail approach to discovery of novel carbonic anhydrase IX inhibitors by simultaneously matching the hydrophobic and hydrophilic halves of the active site.

Dual-tail approach was employed to design novel Carbonic Anhydrase (CA) IX inhibitors by simultaneously matching the hydrophobic and hydrophilic halves of the active site, which also contains a zinc ion as part of the catalytic center. The classic sulfanilamide moiety was used as the zinc binding group. An amino glucosamine fragment was chosen as the hydrophilic part and a cinnamamide fragment as the hydrophobic part in order to draw favorable interactions with the corresponding halves of the active site. In comparison with sulfanilamide which is largely devoid of the hydrophilic and hydrophobic interactions with the two halves of the active site, the compounds so designed and synthesized in this study showed 1000-fold improvement in binding affinity. Most of the compounds inhibited the CA effectively with IC50 values in the range of 7-152 nM. Compound 14e (IC50: 7 nM) was more effective than the reference drug acetazolamide (IC50: 30 nM). The results proved that the dual-tail approach to simultaneously matching the hydrophobic and hydrophilic halves of the active site by linking hydrophobic and hydrophilic fragments was useful for designing novel CA inhibitors. The effectiveness of those compounds was elucidated by both the experimental data and molecular docking simulations. This work laid a solid foundation for further development of novel CA IX inhibitors for cancer treatment.

ß N-O turns and helices induced by ß2-aminoxy peptides: synthesis and conformational studies.

Herein, we report an efficient route for the asymmetric synthesis of ß(2)-aminoxy acids as well as experimental and theoretical studies of conformations of peptides composed of ß(2)-aminoxy acids. The nine-membered-ring intramolecular hydrogen bonds, namely, ß N-O turns, are generated between adjacent residues in those peptides, in accordance with our computational results. The presence of two consecutive homochiral ß N-O turns leads to the formation of ß N-O helical structures in solution, although both helical (composed of two ß N-O turns of the same handedness) and reverse-turn (composed of two ß N-O turns with opposite handedness) structures are of similar stability, as suggested by theoretical studies. Nevertheless, two slightly different conformations, with the same handedness, of ß(2)-aminoxy monomers have been observed in the solid state and in solution according to our X-ray and 2D NOESY studies.