Anti-MCL1 (C-terminal) polyclonal antibody

Dendrobium officinale polysaccharides (DOPs) are carbohydrates predominantly composed of mannose (M1) and glucose, and are known to exhibit antitumour activities. Here, the antitumour properties of carbohydrates including monosaccharide M1, oligosaccharide mannohexaose (M6), and DOPs were investigated. Polysaccharides DOP122, DOP20, DOP8, and DOP2 with molecular weights of 1224.54, 200.99, 80.32, and 24.89 kDa, respectively, were obtained from Dendrobium officinale. Among M1, M6, and DOP122-DOP2, DOP20 exerted the strongest inhibitory effect on the proliferation of osteosarcoma (OS) U2OS and Saos-2 cells. When combined with cisplatin (DDP), DOP20 showed a synergistic inhibition of proliferation. Moreover, DOP20 enhanced DDP-induced cell apoptosis mediated by the mitochondrial pathway by up-regulating P53, Bax, and Bak expression; down-regulating Bcl-2 and Mcl-1 expression; and increasing Cleaved caspase9/Caspase9, Cleaved caspase3/Caspase3, and Cleaved PARP/PARP ratios. These findings confirmed that carbohydrate drugs, especially polysaccharides, used in the treatment of tumours need to be validated in terms of a suitable molecular weight.

Accurate determination of the binding affinity of the ligand to the receptor remains a difficult problem in computer-aided drug design. Here, we study and compare the efficiency of Jarzynski's equality (JE) combined with steered molecular dynamics and the linear interaction energy (LIE) method by assessing the binding affinity of 23 small compounds to six receptors, including beta-lactamase, thrombin, factor Xa, HIV-1 protease (HIV), myeloid cell leukemia-1, and cyclindependent kinase 2 proteins. It was shown that Jarzynski's nonequilibrium binding free energy Delta G(neq)(jar) correlates with the available experimental data with the correlation levels R = 0.89, 0.86, 0.83, 0.80, 0.83, and 0.81 for six data sets, while for the binding free energy Delta G(LIE) obtained by the LIE method, we have R = 0.73, 0.80, 0.42, 0.23, 0.85, and 0.01. Therefore, JE is recommended to be used for ranking binding affinities as it provides accurate and robust results. In contrast, LIE is not as reliable as JE, and it should be used with caution, especially when it comes to new systems.