Mammalian Subtilisin/kexin isozyme SKI-1: a proprotein convertase with a unique cleavage specificity
US7211424B1 · kind B1 · utility
Assignee
Inventors
Key dates
| Filing date | Nov 4, 1999 |
| Grant date | May 1, 2007 |
| Priority date | — |
| Expiry date | Nov 4, 2019 |
Classification
- Technology area (CPC A)Human Necessities
- CPC primaryA61P43/00
- WIPO fieldPharmaceuticals
- WIPO sectorChemistry
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.
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.