Use of anti-aging glycopeptides for inhibition of immune rejection of a graft

A method for inhibition or prevention of immune rejection of a graft comprising the step of:

• a) contacting an isolated graft 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 of the compound of general formula I:
• 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 R3=
• 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 R2=
• 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 R1=
• 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 said graft in said subject in need thereof, said subject in need thereof being under an immune suppressant drug therapy to inhibit or prevent immune rejection of said graft;
• c) discontinue said immune suppressant drug therapy after a time sufficient for implantation of said graft in said subject in need thereof.