Inhibition of cell surface protein disulfide isomerase

Details Inhibition of cell surface protein disulfide isomerase Inhibition of cell surface protein disulfide isomerase

A - Human Necessities

61

K

A61K 31/285 (2006.01) A61K 31/42 (2006.01) A61K 31/555 (2006.01)

Patent

CA 2290005

The invention provides anti-thiol reagents which inhibit enzyme activity of cell-associated protein disulfide isomerase (PDI) by oxidizing or blocking PDI active site vicinal thiol groups which normally participate in disulfide bond rearrangement of PDI substrates. Inhibition of this PDI function is particularly useful in blocking PDI-mediated entry of HIV or other virions into a host cell. The invention further provides an assay for the identification of such PDI inhibitors based on the discovery that inhibitors of the invention also induce shedding of the leucocyte L-selectin adhesion molecule.

L'invention concerne des réactifs anti-thiol qui inhibent l'activité enzymatique d'une protéine disulfure isomérase (PDI) associée à une cellule, par oxydation ou blocage de groupes thiol vicinaux d'un site actif de PDI qui participent normalement à un remaniement de liaison disulfure de supports de PDI. L'inhibition de cette fonction de PDI s'utilise notamment pour bloquer la pénétration par médiation PDI du VIH ou d'autres virions dans une cellule hôte. L'invention concerne également un dosage permettant l'identification de ces inhibiteurs de PDI sur la base de la découverte que les inhibiteurs de la présente invention entraînent également une excrétion de la molécule d'adhésion sélectine L de leucocyte.

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