Improvement in the properties of 3-phenyl-3-trifluoromethyldiazirine based photoreactive bis-glucose probes for GLUT4 following substitution on the phenyl ring.
We have developed two novel 3-phenyl-3-trifluoromethyldiazirinyl bis-glucose derivatives to investigate the properties of the adipocyte glucose transporter GLUT4. These compounds were substituted by electron-withdrawing (iodo and nitro) groups on the aromatic ring of 3-phenyl-3-trifluoromethyldiazirine photophore and were found to be more photosensitive than compounds without such substituents. The compounds were used as inhibitors of insulin-stimulated glucose transport activity in order to assess half-maximal inhibition or relative affinity values for GLUT4. The affinities were found to be 60-130 times higher than the parent compound D-glucose. Because of the increased photo-reactivity and high affinity these compounds will be useful in studies directed at further elucidation of GLUT4 function.
Hashimoto
Makoto
M
Department of Biology and Biochemistry, University of Bath, UK. hasimoto@obihiro.ac.jp
Yang
Jing
J
Hatanaka
Yasumaru
Y
Sadakane
Yutaka
Y
Nakagomi
Kazuya
K
Holman
Geoffrey David
GD
D017667:Adipocytes / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001389:Azirines / Q000737:chemistry* / Q000528:radiation effects; D005947:Glucose / Q000737:chemistry*; D051275:Glucose Transporter Type 4; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008358:Mannose / Q000737:chemistry; D009004:Monosaccharide Transport Proteins / Q000737:chemistry* / Q000378:metabolism; D009124:Muscle Proteins; D010777:Photochemistry; D051381:Rats; D017208:Rats, Wistar; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013056:Spectrophotometry, Ultraviolet; D014466:Ultraviolet Rays
D001389:Azirines; D051275:Glucose Transporter Type 4; D007202:Indicators and Reagents; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495694:Slc2a4 protein, rat; C470119:phenyl-3-trifluoromethyldiazirine; D005947:Glucose; D008358:Mannose