Restriction of Molecular Twisting on a Gold Nanoparticle Surface

To understand the photophysical properties of intramolecular charge transfer (ICT) and twisted intramolecular charge transfer (TICT) states on a gold nanoparticle (Au NP) surface, we have designed and synthesized a new coumarin molecule (C3) that exists both as ICT and TICT states in its excited state in a polar environment. On a Au NP surface, an excited C3 molecule only exists as an ICT state owing to restricted molecular rotation of a diethylamino group; as a result, no conversion from the ICT to TICT state was observed. Selection of the preferential state of a molecule with dual emitting states can be helpful for selected biological applications.     

Osteoporosis detection in postmenopausal women using axial transmission multi-frequency bone ultrasonometer: Clinical findings

The objective of this study was to evaluate if the Bone UltraSonic Scanner (BUSS) can detect osteoporosis in postmenopausal women. BUSS is an axial transmission multi-frequency ultrasonometer for acquisition of wave propagation profiles along the proximal anterior tibia. We derived 10 diagnostically significant BUSS parameters that were then compared with the DXA spine T-score, which was used in this study as the “gold standard” for the assessment of osteoporosis (T-score <−2.5). BUSS wave parameters were studied in 331 postmenopausal women examined by 9 trained operators at 3 clinical sites with use of 3 devices. The efficiency of each BUSS parameter in osteoporosis detection was assessed using a receiver operating characteristic curve analysis. Area under the curve (AUC) for each of 10 parameters ranged from 58.1% to 70.2%. Using these parameters a linear classifier was derived which provided at its output 83.0% AUC, 87.7% sensitivity and 63.2% specificity to DXA-identified osteoporosis. The results of this study confirm BUSS’s capability to detect osteoporosis in postmenopausal women.     

Nonproteinogenic Amino Acid Building Blocks for Nonribosomal Peptide and Hybrid Polyketide Scaffolds

Freestanding nonproteinogenic amino acids have long been recognized for their antimetabolite properties and tendency to be uncovered to reactive functionalities by the catalytic action of target enzymes. By installing them regiospecifically into biogenic peptides and proteins, it may be possible to usher a new era at the interface between small molecule and large molecule medicinal chemistry. Site‐selective protein functionalization offers uniquely attractive strategies for posttranslational modification of proteins. Last, but not least, many of the amino acids not selected by nature for protein incorporation offer rich architectural possibilities in the context of ribosomally derived polypeptides. This Review summarizes the biosynthetic routes to and metabolic logic for the major classes of the noncanonical amino acid building blocks that end up in both nonribosomal peptide frameworks and in hybrid nonribosomal peptide‐polyketide scaffolds.     

Environment-Sensitive Fluorescence of 7-Nitrobenz-2-oxa-1,3-diazol-4-yl (NBD)-Labeled Ligands for Serotonin Receptors

Serotonin is a neurotransmitter that plays a crucial role in the regulation of several behavioral and cognitive functions by binding to a number of different serotonin receptors present on the cell surface. We report here the synthesis and characterization of several novel fluorescent analogs of serotonin in which the fluorescent NBD (7-nitrobenz-2-oxa-1,3-diazol-4-yl) group is covalently attached to serotonin. The fluorescent ligands compete with the serotonin_1A receptor specific radiolabeled agonist for binding to the receptor. Interestingly, these fluorescent ligands display a high environmental sensitivity of their fluorescence. Importantly, the human serotonin_1A receptor stably expressed in CHO-K1 cells could be specifically labeled with one of the fluorescent ligands with minimal nonspecific labeling. Interestingly, we show by spectral imaging that the NBD-labeled ligand exhibits a red edge excitation shift (REES) of 29 nm when bound to the receptor, implying that it is localized in a restricted microenvironment. Taken together, our results show that NBD-labeled serotonin analogs offer an attractive fluorescent approach for elucidating the molecular environment of the serotonin binding site in serotonin receptors. In view of the multiple roles played by the serotonergic systems in the central and peripheral nervous systems, these fluorescent ligands would be useful in future studies involving serotonin receptors.