Human cationic amino acid transporters are not affected by direct nitros(yl)ation

Amino Acids - A direct inhibiting effect of NO on the function of CAT-1 and -2A has been postulated to occur via nitrosylation of cysteine residues in the transporters. Neither the NO donor SNAP...     

Mechanical stresses associated with flattening of human femoropopliteal artery specimens during planar biaxial testing and their effects on the calculated physiologic stress–stretch state

Biomechanics and Modeling in Mechanobiology - Planar biaxial testing is commonly used to characterize the mechanical properties of arteries, but stresses associated with specimen flattening during...     

Precise Gene Editing Preserves Hematopoietic Stem Cell Function following Transient p53-Mediated DNA Damage Response

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Synthesis and biological evaluation of PSMA-targeting paclitaxel conjugates

Prostate cancer (PC) is the second most commonly occurring cancer in men. Conventional chemotherapy has wide variety of disadvantages such as high systemic toxicity and low selectivity. Targeted drug delivery is a promising approach to decrease side effects of therapy. Prostate specific membrane antigen (PSMA) is overexpressed in prostate cancer cells while low level of expression is observed in normal cells. In this study we describe the development of Glu-urea-Lys based PSMA-targeting conjugates with paclitaxel. A series of new PSMA targeting conjugates with paclitaxel was designed and synthesized. The cytotoxicity of conjugates was evaluated against prostate (LNCaP, 22Rv1 and PC-3) and non-prostate (Hek293T, VA13, A549 and MCF-7) cell lines. The most promising conjugate 21 was examined in vivo using 22Rv1 xenograft mice model. It demonstrated good efficiency comparable with paclitaxel, while reduced toxicity. 3D molecular docking study was also performed to understand underlying mechanism of binding and further optimization of the linker substructure and conjugates structure for improving the target affinity. These conjugates may be useful for further design of novel PSMA targeting delivery systems for PC.