On the preparation of carbohydrate-protein conjugates using the traceless Staudinger ligation.
[reaction: see text] The nature of a linker used for preparing glycoconjugate vaccines is of utmost importance as it may lead to immunogenic biomolecules. We report the conjugation of carbohydrate haptens to protein carriers leading to potential vaccines using the traceless Staudinger ligation. The ligation relies on the selective transfer of a phosphane substituent to an azide to form a native amide bond in the final product upon release of an oxidized phosphane byproduct. We designed new phosphino-functionalized cross-linkers suitable for protein carrier derivatization. We evaluated their utility in preparing conjugates using both synthetic and purified bacterial carbohydrates. The use of a borane-protected phosphane which is deprotected at the time of the ligation reaction led to the best results observed thus far in terms of stability toward oxidation and reactivity.
Grandjean
Cyrille
C
Unité de Chimie Organique, URA CNRS 2128 and Unité du Choléra et des Vibrions, Centre National de Référence des Vibrions et du Choléra, Institut Pasteur, 25-28 rue du Docteur Roux, 75724 Paris Cedex 15, France. grandjean.cyr@wanadoo.fr
Boutonnier
Alain
A
Guerreiro
Catherine
C
Fournier
Jean-Michel
JM
Mulard
Laurence A
LA
D006001:Glycoconjugates / Q000138:chemical synthesis*; D006241:Haptens / Q000737:chemistry; D018074:Vaccines, Conjugate / Q000737:chemistry*
D006001:Glycoconjugates; D006241:Haptens; D018074:Vaccines, Conjugate