Metal-free homogeneous catalysed hydrogenation of various imines was accomplished with tris(perfluorophenyl)borane under moderate reaction conditions.

No abstract

With the development of cancer immunotherapy, cancer vaccine has become a novel modality for cancer treatment, and the important role of adjuvant has been realized recently. Chitin, chitosan, and their derivatives have shown their advantages as adjuvants for cancer vaccine. In this paper, the adjuvant properties of chitin and chitosan were discussed, and some detailed information about glycated chitosan and chitosan nanoparticles was also presented to illustrate the trend for future development.

No abstract

This study was initiated to find small molecule ligands that would induce a functional response when docked with neurotrophin Trk receptors. "Minimalist" mimics of β-turns were designed for this purpose. These mimics are: (i) rigid, yet easily folded into turn-like conformations, and (ii) readily accessible from amino acids bearing most of the natural side chains. Gram quantities of sixteen of these turn mimics were prepared, then assembled into 152 fluorescein-labeled bivalent peptidomimetics via a solution-phase combinatorial method. Fluorescence-based screening of these molecules using cells transfected with the Trk receptors identified 10 potential ligands of TrkC, the receptor for neurotrophin-3 (NT-3). Analogs of these bivalent peptidomimetics with biotin replacing the fluorescein label were then prepared and tested to confirm that binding was not due to the fluorescein. Several assays were conducted to find the mode of action of these biotinylated compounds. Thus, direct binding, survival and neuritogenic, and biochemical signal transduction assays showed 8 of the original 10 hits were agonistic ligands binding to the ectodomain of TrkC. Remarkably, some peptidomimetics afford discrete signals leading to either cell survival or neuritogenic differentiation. The significance of this work is three fold. First, we succeeded in finding small, selective, proteolytically stable ligands for the TrkC receptor; there are very few of these in the literature. Second, we show that it is possible to activate distinct and biased signaling pathways with ligands binding at the ectodomain of wild type receptors. Third, the discovery that some peptidomimetics initiate different modes of cell signaling increases their potential as pharmacological probes and therapeutic leads.The neurotrophins are dimeric protein growth factors that help regulate the peripheral and central nervous systems and other tissues that express the Trk and p75 neurotrophin receptors.(1,2) Trk receptors are relatively selective for, and bind with high affinity (∼K d 10 -11 M) to the neurotrophin. Nerve growth factor (NGF) docks with TrkA, Brain Derived Neurotrophic Factor (BDNF) interacts with TrkB(3), and Neurotrophin-3 (NT-3) interacts preferentially with TrkC but can also bind TrkA and TrkB ( Figure 1a). Ligand binding induces phosphorylation (pTyr) of Trk receptors and associated signaling partners and activation of the neurotrophic biological signals: cell growth, cell survival under stress (trophic activity), and/or cellular differentiation (neuritogenic or neurogenic activity).(4-6) * Correspondence regarding design and synthesis of the peptidomimetics to burgess@mail.tamu.edu, and on the biology and pharmacology to uri.saragovi@mcgill.ca. There is also a second receptor for the neurotrophins, p75, a member of the tumor necrosis factor (TNF) receptor superfamily. All the neurotrophins also bind the p75 receptor, but with lesser affinities (10 -9 to 10 -11 M) than for the Trk receptors. (7-9) The p75 receptor can transduce signals which ...