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US 11,826,387 B2Granted
Use of anti-aging glycoprotein for enhancing survival of neurosensory precursor cells
AssigneeProtokinetix Inc.
InventorLachlan Grant Young
Life of this patent
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Abstract
The present disclosure relates to an in vitro method for enhancing engraftment of neurosensory precursor cell comprising the step of contacting an isolated neurosensory precursor cell prior to a transplantation in a subject in need thereof, with a gem-difluorinated C-glycopeptide compound of general formula I, or a pharmaceutically acceptable base, addition salt with an acid, hydrate or solvate thereof:
Claims13
A method for protecting isolated neurosensory precursor cells from prostaglandin E2 toxicity comprising the step of:
- a) contacting an isolated neurosensory precursor cell with a gem-difluorinated C-glycopeptide compound of general formula I, or a pharmaceutically acceptable base, addition salt with an acid, hydrate or solvate thereof, and then washing the isolated neurosensory cells to remove the compound:
- in which:
- N is an integer between 1 and 5,
- R4═H, AA1, or AA1-AA2,
- R5═OH, AA1, or AA1-AA2,
- AA1 and AA2 independently represent amino acids with a non-polar side chain
- and
- R1, R2, R3 are independent groups in which two of R1, R2 and R3 are selected from H, CH3, CH2Ph, CH(CH3)2, CH2CH(CH3)2 or CH(CH3)CH2CH3 and the remaining R1, R2, R3 is
- in which:
- n is an integer between 3 and 4,
- Y, Y′ are independent groups
- in which Y, Y′═H, OR, N3, NR′R″, or SR′″,
- where R═H, benzyl, trimethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl or acetate group,
- R′, R″ independently=H, alkyl, allyl, benzyl, tosylate group, C(═O)-alkyl or C(═O)-Bn,
- R′″═H, alkyl, or acetate group,
- R6 is H, CH3, CH2OH, CH2-glycoside group or CH2—OGP in which GP is a protector group selected from alkyl, benzyl, trimethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, or acetate group,
- R7═OH, OGP′, NH2, N3, NHGP′ or NGP′GP″ in which GP′ and GP″ are independently selected from alkyl, benzyl, trimethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, or acetate group,
- R8 is a hydrogen atom H or a free or protected alcohol function,
- and
- if R1═R2═H, CH3, CH2Ph, CH(CH3)2, CH2CH(CH3)2, or CH(CH3)CH2CH3
- then
- in which:
- n is an integer between 3 and 4,
- Y, Y′ are independent groups
- in which Y, Y′═H, OR, N3, NR′R″, or SR′″,
- where R═H, benzyl, trimethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, or acetate group,
- R′, R″ independently=H, alkyl, allyl, benzyl, tosylate group, C(═O)-alkyl, or C(═O)-Bn,
- R′″═H, alkyl, or acetate group,
- R6 is H, CH3, CH2OH, CH2-glycoside group, or CH2—OGP in which GP is a protector group selected from alkyl, benzyl, trimethylsilyl, tertbutyldimethylsilyl, tert-butyldiphenylsilyl, or acetate group,
- R7═OH, OGP′, NH2, N3, NHGP′, or NGP′GP″ in which GP′ and GP″ are independently selected from alkyl, benzyl, trimethylsilyl, tertbutyldimethylsilyl, tert-butyldiphenylsilyl, or acetate group,
- R8 is a hydrogen atom H or a free or protected alcohol function,
- if R1═R3═H, CH3, CH2Ph, CH(CH3)2, CH2CH(CH3)2, or CH(CH3)CH2CH3
- then
- in which:
- n is an integer between 3 and 4,
- Y, Y′ are independent groups
- in which Y, Y′═H, OR, N3, NR′R″, or SR′″,
- where R═H, benzyl, trimethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, or acetate group,
- R′, R″ independently=H, alkyl, allyl, benzyl, tosylate group, C(═O)-alkyl, or C(═O)-Bn,
- R′″═H, alkyl, or acetate group,
- R6 is H, CH3, CH2OH, CH2-glycoside group, or CH2—OGP in which GP is a protector group selected from alkyl, benzyl, trimethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, or acetate group,
- R7═OH, OGP′, NH2, N3, NHGP′, or NGP′GP″ in which GP′ and GP″ are independently selected from alkyl, benzyl, trimethylsilyl, tertbutyldimethylsilyl, tert-butyldiphenylsilyl, or acetate group,
- R8 is a hydrogen atom H or a free or protected alcohol function,
- if R2═R3═H, CH3, CH(CH3)2, CH2CH(CH3)2, or CH(CH3)CH2CH3
- then
- in which:
- n is an integer between 3 and 4,
- Y, Y′ are independent groups
- in which Y, Y′H, OR, N3, NR′R″, or SR′″,
- where R═H, benzyl, trimethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, or acetate group,
- R′, R″ independently=H, alkyl, allyl, benzyl, tosylate group, C(═O)-alkyl, or C(═O)-Bn,
- R′″═H, alkyl, or acetate group,
- R6 is H, CH3, CH2OH, CH2-glycoside group, or CH2—OGP in which GP is a protector group selected from alkyl, benzyl, trimethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, or acetate group,
- R7═OH, OGP′, NH2, N3, NHGP′, or NGP′GP″ in which GP′ and GP″ are independently selected from alkyl, benzyl, trimethylsilyl, tertbutyldimethylsilyl, tert-butyldiphenylsilyl, or acetate group,
- R8 is a hydrogen atom H or a free or protected alcohol function
- b) transplanting the treated isolated neurosensory precursor cells of step a) in a subject in need thereof,
- wherein said compound protects said isolated neurosensory precursor cell from prostaglandin E2 toxicity and wherein the method comprises no step where said isolated neurosensory precursor cells are cryopreserved.
54 more elements
Dependencies are inferred from the claim text.