PACE4, a member of the proprotein convertases (PCs) family of serine proteases, is a validated target for prostate cancer. Our group has developed a potent and selective PACE4 inhibitor: Ac-LLLLRVKR-NH . In seeking for modifications to increase the selectivity of this ligand toward PACE4, we replaced one of its P3 Val methyl groups with a basic group capable of forming a salt bridge with D160 of PACE4. The resulting inhibitor is eight times more potent than the P3 Val parent inhibitor and two times more selective over furin, because the equivalent salt bridge with furin E257 is not optimal. Moreover, the β-branched nature of the new P3 residue favors the extended β-sheet conformation usually associated with substrates of proteases. This work provides new insight for better understanding of β-sheet backbone-backbone interactions between serine proteases and their peptidic ligands.
Compression molding is a current technique in polymer processing. Despite numerous studies, effect of molding pressure on physical properties has surprisingly not been fully investigated. In this study, the thermal and mechanical behavior of the compression-molded polyethylene were thus explored to better grasp the relationship between processing parameters and ensuing properties. The effect of the molding temperature, pressure, cooling rate, and temperature profile on the tensile and flexural moduli as well as melting point of polyethylene was studied. We conclude that higher tensile and flexural moduli are obtained by increasing pressure and molding temperature, as well as decreasing the cooling rate. Our results were corroborated by X-ray diffraction and differential scanning calorimetry measurements. Moreover, the use of a temperature gradient with different temperatures for the upper and bottom plates of the mold leads to asymmetric samples whose tensile and flexural moduli are improved. V C 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46176.
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