Use of anti-aging glycopeptides to enhance pancreatic cell health, survival and improve transplant outcome 机翻标题: 暂无翻译,请尝试点击翻译按钮。

公开号/公开日
WO2015184544 A1 2015-12-10 [WO2015184544] / 2015-12-10
申请号/申请日
2015WO-CA50509 / 2015-06-02
发明人
SHAPIRO A M JAMES;YOUNG LACHLAN GRANT;
申请人
PROTOKINETIX;
主分类号
IPC分类号
A61K-035/39A61K-038/14A61L-027/38A61P-003/10C07K-009/00C12N-005/071
摘要
(WO2015184544) The present disclosure relates to an in vitro method for enhancing engraftment of isolated pancreatic cells comprising the step of contacting an isolated pancreatic 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 of the compound of general formula I :
机翻摘要
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地址
代理人
代理机构
;
优先权号
2014US-62007626 2014-06-04
主权利要求
(WO2015184544)  1. An in vitro method for enhancing engraftment of isolated pancreatic cells, isolated pancreatic progenitor cells, or both comprising the step of: a) contacting an isolated pancreatic cell, an isolated pancreatic progenitor cell, or both 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, h drate or solvate of the compound of general formula I : in which: N is an integer between 1 and 5, R4= H, AAi, or AA AA2, R5= OH, AAi, or AA AA2, AAi 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-butyl dimethylsilyl, tert- butyldiphenylsilyl or acetate group, R', R" independently = H, alkyl, allyl, benzyl, tosylate group, C(=0)- alkyl or C(=0)-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-butyl dimethylsilyl, 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-butyl dimethylsilyl, tert-butyldiphenylsilyl, or acetate group, R8 is a hydrogen atom H or a free or protected alcohol function, and if RI= 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-butyl dimethylsilyl, tert-butyldiphenylsilyl, or acetate group, R', R" independently = H, alkyl, allyl, benzyl, tosylate group, C(=0)-alkyl, or C(=0)-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, if RI= R3= H, CH3, ChbPh, 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-butyl dimethylsilyl, tert-butyldiphenylsilyl, or acetate group, R', R" independently = H, alkyl, allyl, benzyl, tosylate group, C(=0)-alkyl, or C(=0)-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-butyl dimethylsilyl, 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, if H, CH3, CH(CH3)2, CH2CH(CH3)2, or CH(CH3)CH2CH3 then R1= Y' 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-butyl dimethylsilyl, tert-butyldiphenylsilyl, or acetate group, R', R" independently = H, alkyl, allyl, benzyl, tosylate group, C(=0)-alkyl, or C(=0)-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-butyl dimethylsilyl, tert- butyldiphenylsilyl, or acetate group, R7 = OH, OGP', NH2, N.3, 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.  2. An in vitro method for improving the insulin secretory function of isolated pancreatic beta cells prior to transplantation in a subject in need thereof, comprising the step of: a) contacting an isolated pancreatic beta 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 of the compound of general formula I : in which: N is an integer between 1 and 5, AAi 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-butyl dimethylsilyl, tert- butyldiphenylsilyl or acetate group, R', R" independently = H, alkyl, allyl, benzyl, tosylate group, C(=0)- alkyl or C(=0)-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-butyl dimethylsilyl, 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-butyl dimethylsilyl, tert-butyldiphenylsilyl, or acetate group, R8 is a hydrogen atom H or a free or protected alcohol function, and if H, CH3, ChbPh, 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-butyl dimethylsilyl, tert-butyldiphenylsilyl, or acetate group, R', R" independently = H, alkyl, allyl, benzyl, tosylate group, C(=0)-alkyl, or C(=0)-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, 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-butyl dimethylsilyl, tert-butyldiphenylsilyl, or acetate group, R', R" independently = H, alkyl, allyl, benzyl, tosylate group, C(=0)-alkyl, or C(=0)-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-butyl dimethylsilyl, 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, if 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-butyl dimethylsilyl, tert-butyldiphenylsilyl, or acetate group, R', R" independently = H, alkyl, allyl, benzyl, tosylate group, C(=0)-alkyl, or C(=0)-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-butyl dimethylsilyl, 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.  3. An in vitro method for protecting isolated pancreatic cells, isolated pancreatic progenitor cells, or both from immunosuppressant drug toxicity prior to a transplantation in a subject in need thereof comprising the step of: a) contacting an isolated pancreatic cell, an isolated pancreatic progenitor cell, or both 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, AAi 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-butyl dimethylsilyl, tert- butyldiphenylsilyl or acetate group, R', R" independently = H, alkyl, allyl, benzyl, tosylate group, C(=0)- alkyl or C(=0)-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-butyl dimethylsilyl, 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-butyl dimethylsilyl, tert-butyldiphenylsilyl, or acetate group, R8 is a hydrogen atom H or a free or protected alcohol function, and if RI= 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-butyl dimethylsilyl, tert-butyldiphenylsilyl, or acetate group, R', R" independently = H, alkyl, allyl, benzyl, tosylate group, C(=0)-alkyl, or C(=0)-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, tert butyldimethylsilyl, tert-butyldiphenylsilyl, or acetate group, R8 is a hydrogen atom H or a free or protected alcohol function, if RI= R3= H, CH3, ChbPh, 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-butyl dimethylsilyl, tert-butyldiphenylsilyl, or acetate group, R', R" independently = H, alkyl, allyl, benzyl, tosylate group, C(=0)-alkyl, or C(=0)-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-butyl dimethylsilyl, 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, if H, CH3, CH(CH3)2, CH2CH(CH3)2, or CH(CH3)CH2CH3 then R1= Y' 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-butyl dimethylsilyl, tert-butyldiphenylsilyl, or acetate group, R', R" independently = H, alkyl, allyl, benzyl, tosylate group, C(=0)-alkyl, or C(=0)-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-butyl dimethylsilyl, tert- butyldiphenylsilyl, or acetate group, R7 = OH, OGP', NH2, N.3, 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.  4. An in vitro method for decreasing an inflammatory response of isolated pancreatic cells, isolated pancreatic progenitor cells, or both prior to a transplantation in a subject in need thereof comprising the step of: a) contacting an isolated pancreatic cell, an isolated pancreatic progenitor cell, or both with a gem-difluorinated C-glycopeptide compound of general formula I, or a pharmaceutically acceptable base, addition salt with an acid, hydrate or solvate compound of general formula I : (I) in which: N is an integer between 1 and 5, AAi 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, Ch Ph, 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-butyl dimethylsilyl, tert- butyldiphenylsilyl or acetate group, R', R" independently = H, alkyl, allyl, benzyl, tosylate group, C(=0)- alkyl or C(=0)-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-butyl dimethylsilyl, 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-butyl dimethylsilyl, tert-butyldiphenylsilyl, or acetate group, R8 is a hydrogen atom H or a free or protected alcohol function, and if H, CH3, ChbPh, 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-butyl dimethylsilyl, tert-butyldiphenylsilyl, or acetate group, R', R" independently = H, alkyl, allyl, benzyl, tosylate group, C(=0)-alkyl, or C(=0)-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, 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-butyl dimethylsilyl, tert-butyldiphenylsilyl, or acetate group, R', R" independently = H, alkyl, allyl, benzyl, tosylate group, C(=0)-alkyl, or C(=0)-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-butyl dimethylsilyl, 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, if 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(=0)-alkyl, or C(=0)-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-butyl dimethylsilyl, 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.  5. A method of transplanting isolated pancreatic cells, isolated pancreatic progenitor cells, or both in a subject in need thereof comprising the steps of : a) contacting an isolated pancreatic cell, an isolated pancreatic progenitor cell, or both 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, AAi, or AA AA2, R5= OH, AAi, or AA AA2, AAi 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-butyl dimethylsilyl, tert- butyldiphenylsilyl or acetate group, R', R" independently = H, alkyl, allyl, benzyl, tosylate group, C(=0)- alkyl or C(=0)-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-butyl dimethylsilyl, 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-butyl dimethylsilyl, tert-butyldiphenylsilyl, or acetate group, R8 is a hydrogen atom H or a free or protected alcohol function, and if RI= 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-butyl dimethylsilyl, tert-butyldiphenylsilyl, or acetate group, R', R" independently = H, alkyl, allyl, benzyl, tosylate group, C(=0)-alkyl, or C(=0)-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, if RI= R3= H, CH3, ChbPh, 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-butyl dimethylsilyl, tert-butyldiphenylsilyl, or acetate group, R', R" independently = H, alkyl, allyl, benzyl, tosylate group, C(=0)-alkyl, or C(=0)-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-butyl dimethylsilyl, 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, if H, CH3, CH(CH3)2, CH2CH(CH3)2, or CH(CH3)CH2CH3 then R1= Y' 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, tnmethylsilyl, tert-butyl dimethylsilyl, tert-butyldiphenylsilyl, or acetate group, R', R" independently = H, alkyl, allyl, benzyl, tosylate group, C(=0)-alkyl, or C(=0)-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, tnmethylsilyl, tert-butyl dimethylsilyl, tert- butyldiphenylsilyl, or acetate group, R7 = OH, OGP', NH2, N.3, NHGP', or NGP'GP" in which GP' and GP" are independently selected from alkyl, benzyl, tnmethylsilyl, tert butyldimethylsilyl, tert-butyldiphenylsilyl, or acetate group, . R8 is a hydrogen atom H or a free or protected alcohol function; b) transplanting the treated isolated pancreatic cell of step a) in said subject in need thereof.  23. An isolated pancreatic cell, an isolated pancreatic progenitor cell, or both contacted 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, AAi 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, ChbPh, 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-butyl dimethylsilyl, tert- butyldiphenylsilyl or acetate group, R', R" independently = H, alkyl, allyl, benzyl, tosylate group, C(=0)- alkyl or C(=0)-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-butyl dimethylsilyl, 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-butyl dimethylsilyl, tert-butyldiphenylsilyl, or acetate group, R8 is a hydrogen atom H or a free or protected alcohol function, and if RI= R2= H, CH3, ChbPh, CH(CH3)2, CH2CH(CH3)2, or CH(CH3)CH2CH3 then R3= R' 6 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-butyl dimethylsilyl, tert-butyldiphenylsilyl, or acetate group, R', R" independently = H, alkyl, allyl, benzyl, tosylate group, C(=0)-alkyl, or C(=0)-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, 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-butyl dimethylsilyl, tert-butyldiphenylsilyl, or acetate group, R', R" independently = H, alkyl, allyl, benzyl, tosylate group, C(=0)-alkyl, or C(=0)-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-butyl dimethylsilyl, 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, if 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, tnmethylsilyl, tert-butyl dimethylsilyl, tert-butyldiphenylsilyl, or acetate group, R', R" independently = H, alkyl, allyl, benzyl, tosylate group, C(=0)-alkyl, or C(=0)-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, tnmethylsilyl, tert-butyl dimethylsilyl, 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, tnmethylsilyl, tert butyldimethylsilyl, tert-butyldiphenylsilyl, or acetate group, . R8 is a hydrogen atom H or a free or protected alcohol function.  30. Use of 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, for enhancing engraftment of isolated pancreatic cells, isolated pancreatic progenitor cells, or both in a subject in need thereof: in which: N is an integer between 1 and 5, AAi 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, CH2PI-1, 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-butyl dimethylsilyl, tert- butyldiphenylsilyl or acetate group, R', R" independently = H, alkyl, allyl, benzyl, tosylate group, C(=0)- alkyl or C(=0)-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-butyl dimethylsilyl, 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-butyl dimethylsilyl, tert-butyldiphenylsilyl, or acetate group, R8 is a hydrogen atom H or a free or protected alcohol function, and if RI= 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-butyl dimethylsilyl, tert-butyldiphenylsilyl, or acetate group, R', R" independently = H, alkyl, allyl, benzyl, tosylate group, C(=0)-alkyl, or C(=0)-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, if RI= R3= H, CH3, ChbPh, 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-butyl dimethylsilyl, tert-butyldiphenylsilyl, or acetate group, R', R" independently = H, alkyl, allyl, benzyl, tosylate group, C(=0)-alkyl, or C(=0)-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-butyl dimethylsilyl, 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, if H, CH3, CH(CH3)2, CH2CH(CH3)2, or CH(CH3)CH2CH3 then R1= Y' 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-butyl dimethylsilyl, tert-butyldiphenylsilyl, or acetate group, R', R" independently = H, alkyl, allyl, benzyl, tosylate group, C(=0)-alkyl, or C(=0)-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-butyl dimethylsilyl, tert- butyldiphenylsilyl, or acetate group, R7 = OH, OGP', NH2, N.3, 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.  31. Use of 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, for improving the insulin secretory function of isolated pancreatic beta cells, isolated pancreatic progenitor cells, or both prior to transplantation in a subject in need thereof: in which: N is an integer between 1 and 5, AAi 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, ChbPh, 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-butyl dimethylsily(...)
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