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This undergraduate organic laboratory experiment consists of three different reactions occurring in the same flask: a cycloaddition reaction, preceded by decarboxylation and nucleophilic substitution reactions. The decarboxylation and cycloaddition reactions occur using identical Cu(I) catalyst and conditions. Orange, lemon, and other citrus fruit peels and juices in the presence of CuSO[subscript 4] lead to the Cu(I)-catalyzed decarboxylation of 3-phenyl-2-propynoic acid to give ethynylbenzene. These click chemistry conditions give Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) of 2-azido-1-phenylethanone with ethynylbenzene to afford 1-phenyl-2-(4-phenyl-1"H"-1,2-3-triazol-1-yl)ethanone regioselectively. (Contains 1 table and 1 scheme.)

Membrane-type I matrix metalloproteinases (MT1-MMP) is an enzyme critical to the remodeling and homeostasis of extracellular matrix, and when over expressed it contributes to metastasis and cancer cell progression. Because of its role and implication as a biomarker that is upregulated in various cancers, MT1-MMP has become an attractive target for drug discovery. A small pilot library of peptidomimetics containing a phosphoramidate core as a zinc-binding group was synthesized and tested for inhibitory potency against MT1-MMP. From this library, a novel two residue peptidomimetic scaffold was identified that confers potency against MT1-MMP at submicromolar concentrations. The results of this study confirm that for this scaffold, valine is favored as a P1 residue and leucine in the P1′ position. Furthermore, steric tolerance was observed for theN-terminus, thus implicating that a second-generation library could be constructed to extend the scaffold to P2 without concomitant loss of affinity within the MT1-MMP catalytic domain. [ABSTRACT FROM AUTHOR]

Understanding the molecular mechanism of prostate cancer progression from androgen dependence to independence may lead to developing more effective treatments against prostate cancer. Herein, our previous in vitro model was employed to assess the effects of continuous androgen-deprivation on developing the metastatic phenotype from androgen-dependent prostate cancer cells (LNCaP). The results indicated that long-term androgen deprivation resulted in overexpression of calpain 2 and increased expression of filamin A (FlnA), but not for calpain 1. The enhanced activity of calpain 2 was confirmed by the accumulation of cleaved FlnA fragments, which could be effectively blocked by calpeptin (an inhibitor of calpain 2). Therefore, the combination of calpain 2 inhibitor and androgen deprivation may provide new therapeutic strategy for patients to prevent or postpone prostate cancer progression.