Chemistry: molecular biology and microbiology – Enzyme – proenzyme; compositions thereof; process for... – Hydrolase
Reexamination Certificate
2007-05-01
2007-05-01
Nashed, Nashaat T. (Department: 1656)
Chemistry: molecular biology and microbiology
Enzyme , proenzyme; compositions thereof; process for...
Hydrolase
C435S068100, C435S069100, C435S252300, C435S320100, C530S350000, C530S326000, C530S327000, C536S023100, C536S023200
Reexamination Certificate
active
09830837
ABSTRACT:
Using RT-PCR and degenerate oligonucleotides derived from the active site residues of subtilisin-kexin-like serine proteinases, we have identified a highly conserved and phylogenetically ancestral human, rat and mouse type-I membrane-bound proteinase called subtilisin-kexin-isozyme-1 (SKI-1). Computer data bank searches reveals that human SKI-1 was previously cloned but with no identified function. A SKI-1 processed fragment is secreted in culture media in a soluble form. In vitro studies suggest that SKI-1 is a Ca2+-dependent serine proteinase exhibiting a wide pH optimum for cleavage of proBDNF. Peptides mimicking SKI-1 cleavages sites are also disclosed. SKI-1 prosegment has an ex vivo inhibitory effect on SKI-1 activity. The prosegment is also processed and secreted in culture media. One of its fragments is found tightly associated with the SKI-1 soluble form. Therapeutic applications for SKI-1 inhibitors are disclosed.
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Edwa
Chretien Michel
Marcinkiewicz Mieczyslaw
Seidah Nabil G.
Institut de Recherches Cliniques de Montreal
Moore William W.
Nashed Nashaat T.
Quarles & Brady LLP
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