Synthesis of a pyridoxine-peptide based delivery system for nucleotides.
As a first step in the development of a nucleotide delivery system making use of oligopeptide permease, we have synthesized pyridoxine-peptide-nucleotide conjugates. The nucleotides are bonded on serine residues. The peptides terminate with a pyroglutamate residue. In the first example, the pyridoxine moiety is connected at the end of the peptides, while, in the second example, the pyridoxine moiety is bonded at an aspartic acid residue in a middle position of the peptide. Nucleotides are introduced as phosphoramidites. The synthetic strategy involves a series of protection, deprotection, and coupling reactions, and integrates peptide, nucleotide, and pyridoxine chemistry. The final deprotection step was carried out in basic conditions using 10% K2CO3 in MeOH.
Marchand
Arnaud
A
Laboratory of Medicinal Chemistry, Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
Marchand
Damien
D
Busson
Roger
R
Marlière
Philipe
P
Herdewijn
Piet
P
D002626:Chemistry, Pharmaceutical / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods*; D009711:Nucleotides / Q000008:administration & dosage / Q000138:chemical synthesis*; D010455:Peptides / Q000008:administration & dosage / Q000138:chemical synthesis*; D011736:Pyridoxine / Q000008:administration & dosage / Q000138:chemical synthesis*
D009711:Nucleotides; D010455:Peptides; D011736:Pyridoxine