J Appl Biomater Funct Mater
December 2015
Purpose: To develop and characterize a microscale pectin-oligochitosan hydrogel microcapsule system that could be applied in such biological fields as drug delivery, cell immobilization/encapsulation, and tissue engineering.
Methods: Microscale pectin-oligochitosan hydrogel microcapsules were prepared by using the vibration/electrostatic spray method. The morphology and chemistry of the hydrogel microcapsules were characterized by using scanning electron microscope (SEM) and Fourier Transform Infrared Spectroscopy (FTIR), respectively.
Several protein engineering approaches were combined to optimize the selectivity and activity of Vibrio fluvialis aminotransferase (Vfat) for the synthesis of (3S,5R)-ethyl 3-amino-5-methyloctanoate; a key intermediate in the synthesis of imagabalin, an advanced candidate for the treatment of generalized anxiety disorder. Starting from wild-type Vfat, which had extremely low activity catalyzing the desired reaction, we engineered an improved enzyme with a 60-fold increase in initial reaction velocity for transamination of (R)-ethyl 5-methyl 3-oxooctanoate to (3S,5R)-ethyl 3-amino-5-methyloctanoate. To achieve this, <450 variants were screened, which allowed accurate assessment of enzyme performance using a low-throughput ultra performance liquid chromatography assay.
View Article and Find Full Text PDFThe amphiphilic gadolinium complex MS-325 ((trisodium-{(2-(R)-[(4,4-diphenylcyclohexyl) phosphonooxymethyl] diethylenetriaminepentaacetato) (aquo)gadolinium(III)}) is a contrast agent for magnetic resonance angiography (MRA). MS-325 comprises a GdDTPA core with an appended phosphodiester moiety linked to a diphenylcyclohexyl group to facilitate noncovalent binding to serum albumin and extension of the plasma half-life in vivo. The chiral DTPA ligand (R) was derived from L-serine, and upon complexation with gadolinium, forms two interconvertible diastereomers, denoted herein as isomers A and B.
View Article and Find Full Text PDFA mutational analysis of the femtomolar-affinity anti-fluorescein antibody 4M5.3, compared to its wild-type progenitor, 4-4-20, indicates both context-dependent and -independent mutations are responsible for the 1800-fold affinity improvement. 4M5.
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