Synthesis and biological activity of ribose-5 '-carbamate derivatives of vitamin B-12

Twelve biologically active derivatives of vitamin B-12 (cyanocobalamin) hav e been synthesized in which spacers were attached to the ribose-5'-hydroxyl group of vitamin B-12. Their potential to act as oral delivery agents for proteins, nanospheres, or immunogens using the vitamin B-12 uptake system w as evaluated by determining their affinity for intrinsic factor (IF) and no n-IF. The ribose-5'-hydroxyl group of vitamin B-12 was activated through th e use of 1,1'-carbonyldiimidazole (CDI), 1,1'-carbonyldi(1,2,4-triazole) (C DT), or di(1-benzotriazolyl) carbonate (DBTC). Subsequent addition of an am inoalkane, diaminoalkane, or alkane diacid dihydrazide gave rise to vitamin B12 derivatives suitable for attachment to various proteins, peptides, or nanospheres to enable oral delivery utilizing the vitamin B12 uptake system . The ribose-5'-carbamate derivatives were found to possess similar affinit y for intrinsic factor as that of the e-monocarboxylic acid of vitamin B-12 . The affinity for non-IF was similar to cyanocobalamin or even higher for some of the smaller derivatives. Polysciences nanoparticles derivatized wit h vitamin B-12 5'-carbamate adipic dihydrazide into CaCo-2 cells showed sig nificantly higher levels of transport of the particles, when compared to un modified particles.