Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.1 (chymotrypsin)
 10,938 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human neurotrophin-3 (NT-3) is a member of the nerve growth factor (NGF) family of neurotrophic factors, and the recombinant protein is being developed as a therapeutic for neurodegenerative diseases. The final product purity and lot-to-lot variation are monitored routinely by peptide mapping. However, only the N-terminal region of NT-3 was susceptible to proteolysis under native conditions. Complete digestion required that the protein be chemically modified by reduction and S-alkylation prior to proteolysis. Complete proteolytic degradation of the protein was achieved simply by an initial denaturation of NT-3 in 6 M guanidinium chloride (pH6) for 2 hr at 37 degrees C, followed by a tenfold dilution with the digestion buffer (0.1 M Tris-HCl, 1 mM CaCl2 at pH 7.0) and immediate addition of chymotrypsin at 1% by weight. Direct comparison of the peptide map with an identical aliquot that had been reduced and alkylated also allowed the establishment of the cystine linkages present in NT-3: Cys14 to Cys79, Cys57 to Cys108, and Cys67 to Cys110. This disulfide structure is homologous to the NGF family of neurotrophic factors.
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PMID:Human neurotrophin-3: a one-step peptide mapping method and complete disulfide characterization of the recombinant protein. 881 11

We report the development of a series of physical hydrogel blends composed of hyaluronan (HA) and methyl cellulose (MC) designed for independent delivery of one or more drugs, from 1 to 28 days, for ultimate application in spinal cord injury repair strategies. To achieve a diversity of release profiles we exploit the combination of fast diffusion-controlled release of dissolved solutes from the HAMC itself and slow drug release from poly(lactide-co-glycolide) particles dispersed within the gel. Delivery from the composite hydrogels was demonstrated using the neuroprotective molecules NBQX and FGF-2, which were released for 1 and 4 days, respectively; the neuroregenerative molecules dbcAMP and EGF, and proteins alpha-chymotrypsin and IgG, which were released for 28 days. alpha-chymotrypsin and IgG were selected as model proteins for the clinically relevant neurotrophin-3 and anti-NogoA. Particle loaded hydrogels were significantly more stable than HAMC alone and drug release was longer and more linear than from particles alone. The composite hydrogels are minimally swelling and injectable through a 30 gauge/200 microm inner diameter needle at particle loads up to 15 wt.% and particle diameters up to 15 microm.
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PMID:An injectable drug delivery platform for sustained combination therapy. 1944 92