Novel glycosynthons for glycoconjugate preparation: oligosaccharylpyroglutamylanilide derivatives.
The reducing sugar of an oligosaccharide reacting with the alpha-amino group of an amino acid is converted to an N-oligosaccharylamino acid which can then be stabilized by N-acylation. Oligosaccharides in solution in N,N-dimethylformamide reacted with alpha-glutamyl-p-nitroanilide at 50 degrees C for a few hours, leading to an N-oligosaccharylglutamyl-p-nitroanilide. Then, the gamma-carboxylic group of the glutamyl moiety, activated by adding (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP), reacted with the substituted alpha-amino group of the glutamyl residue, leading to an N-oligosaccharylpyroglutamyl-p-nitroanilide within 0.5 h. Such a one-pot two-step reaction was shown to be very efficient in the case of a disaccharide such as lactose, or pentasaccharides such as lacto-N-fucopentaoses, Lewis(a) or Lewis(x). The glycosynthons were characterized by chromatography (HPAEC and HPLC); their molecular mass was determined by electrospray ionization mass spectrometry, and the glycosylamides were shown to have a beta-anomeric configuration on the basis of their proton NMR. The N-oligosaccharylpyroglutamyl-p-nitroanilides are quite stable at room temperature over a large pH range. They are easily converted to N-oligosaccharylpyroglutamyl-p-isothiocyanatoanilides which can be used to prepare glycoconjugates such as cationic glycosylated polylysines suitable for specifically delivering genes or oligonucleotides in a sugar-dependent manner.
Quétard
C
C
Glycobiologie, Centre de Biophysique Moléculaire, CNRS and Université d'Orleans, France.
Bourgerie
S
S
Normand-Sdiqui
N
N
Mayer
R
R
Strecker
G
G
Midoux
P
P
Roche
A C
AC
Monsigny
M
M
D015119:Aminocaproic Acid / Q000737:chemistry; D000813:Anilides / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004126:Dimethylformamide / Q000737:chemistry; D004355:Drug Stability; D018698:Glutamic Acid / Q000737:chemistry; D006001:Glycoconjugates / Q000138:chemical synthesis*; D007700:Kinetics; D007785:Lactose / Q000737:chemistry; D007983:Lewis Blood Group Antigens / Q000737:chemistry; D016256:Lewis X Antigen / Q000737:chemistry; D013058:Mass Spectrometry; D009844:Oligosaccharides / Q000737:chemistry*; D011761:Pyrrolidonecarboxylic Acid / Q000737:chemistry*
D000813:Anilides; D006001:Glycoconjugates; D007983:Lewis Blood Group Antigens; D016256:Lewis X Antigen; D009844:Oligosaccharides; D018698:Glutamic Acid; D004126:Dimethylformamide; D007785:Lactose; D011761:Pyrrolidonecarboxylic Acid; D015119:Aminocaproic Acid