Syntheses of functionalized biotin N-1' derivatives: new tools for the control of gene expression with small molecules.
The exceptionally high affinity of biotin toward avidin and streptavidin is at the basis of (strept)avidin-biotin biotechnology, which has numerous applications in life sciences. Recent biotin developments for in vivo and in vitro acylation of selective targeted protein and intein-mediated site specific protein biotinylation require the free biotin carboxyl function to covalently bind with the targeted protein. However, recently this carboxylic function has been used to substitute biotin with numerous ligands and flags. In the present work, we propose the N-1' labeling possibilities of biotin, keeping the valeric chain free. We describe liquid and solid-phase syntheses of functionalized biotin N-1' derivatives. Although the N-1' modification involves a two-log decrease in affinity, in vitro these molecules kept their high avidin affinity (around 10(-12) M) and the in vivo acylation ability of new biotin derivatives.
Inard
Cyril
C
INSERM U563, C. P. T. P., Département Innovation Thérapeutique et Oncologie Moléculaire, Institut Claudius Regaud, 20-24 rue du pont Saint Pierre, 31052 Toulouse Cédex, France.
Fourcade
Emmanuelle
E
Baron
Rudi
R
Tovar
Daniel
D
Chaisemartin
Laurent
L
Blonski
Casimir
C
Faye
Jean-Charles
JC
D001483:Base Sequence; D001710:Biotin / Q000138:chemical synthesis* / Q000737:chemistry; D017931:DNA Primers; D005786:Gene Expression Regulation / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D016133:Polymerase Chain Reaction; D016339:Spectrometry, Mass, Fast Atom Bombardment
D017931:DNA Primers; D001710:Biotin