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The compounds can also make numerous hydrogen bonds, polar contacts and p-p stacking interactions with hPC6 active site residues. The G, R1, R2 and R3 substituents of the di-aryl 2,5-dideoxystreptamine compounds 1e, 1f and 1g can occupy one or more of the sub-pockets S1, S2 and S4 and also the region near the catalytic triad. In contrast, the G, R1, R2 and R3 substituents of the tri-aryl 2,5-dideoxystreptamine compounds compounds 1n and 1o are able to occupy the S1, S2 and S3 sub-pockets, in addition to the region near the catalytic triad. Acetylene-linker-Val-Cit-PABC-MMAE customer reviews compound 1n can also occupy the S4 sub-pocket; however, the physical size of the 3 naphthyl rings prevent compound 1o from doing so. The binding modes for the five compounds in the hPC6 active site were consistent with the binding mode of compound 1n in human furin described previously by Jiao et al. Decidualization of HESCs is a cellular process essential for embryo implantation. PC6 is critical for decidualization and blocking of PC6 activity inhibits the process. To determine whether the five compounds would also inhibit PC6-dependent decidualization, HESCs were cultured without or with 10 mM of each compound in the presence of decidualizing stimuli. Using prolactin as the decidual marker, of the five compounds, only compound 1o significantly inhibited decidualization, whereas the other four compounds had no effect. One of the known mechanisms of PC6 action in regulating endometrial epithelial cell receptivity is through the cleavage of pro-integrin-aV into its functional heavy and light chains. To further establish that compound 1o reduced Ishikawa cell receptivity to spheroid attachment through PC6 inhibition, total cell proteins were analysed for pro-integrin-aV cleavage by western blot. Briciclib Although both the proform and the heavy chain of integrin-aV were detected in all cell lysates, the relative amount of each form was clearly different between control and compound 1o-treated cel

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Author: calcimimeticagent