Artificial metalloglycoclusters: compact saccharide shell to induce high lectin affinity as well as strong luminescence.
Tris-bipyridine ferrous and ruthenium complexes carrying various saccharide appendages have been investigated to develop sensory systems for monitoring saccharide-binding phenomena. Ferrous O-glycoclusters having spacer moieties inserted between saccharide appendages and the complex core showed enhanced affinities to lectins, but ferrous N-glycoclusters, in which the saccharide-appendages are directly linked to the complex core via amide linkage, had low lectin-affinities. Molecular dynamics calculation indicated that the O-glycoclusters have flexible and densely packed saccharide clusters, in contrast to the octahedrally fixed saccharide arrays of N-glycoclusters. Flexibility of saccharide clusters is essential for their enhanced affinity, probably to induce conformational change to fit the recognition sites of lectins. According to these insights, ruthenium O-glycoclusters have been designed as luminescence biosensors. The ruthenium complexes carrying alpha-manno clusters exhibited excellent affinities (IC(min) = 9.0 x 10(-)(8) M) to concanavalin A (ConA). It is suggested from conformational analysis that densely packed mannoclusters can be fit properly to the recognition site of ConA. The binding was enthalpicaly driven (deltaH degrees = -21.8 kcal/mol). This binding behavior is quite similar to that of 1-3/1-6 trimannoside to ConA. They have strongly amplified luminescence (Phi(em) = 0.15), and their luminescence intensities were changed (approximately 40%) upon binding to the specific lectins. The ruthenium glycoclusters can be a suitable sensory system for saccharide-binding phenomena.
Hasegawa
Teruaki
T
Department of Molecular Design, Graduate School of Engineering, Nagoya University, Chikusa, Nagoya 464-8603, Japan.
Yonemura
Takahiro
T
Matsuura
Kazunori
K
Kobayashi
Kazukiyo
K
D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D001665:Binding Sites; D002942:Circular Dichroism; D004187:Disaccharides / Q000737:chemistry*; D006001:Glycoconjugates / Q000737:chemistry*; D007501:Iron / Q000737:chemistry; D037102:Lectins / Q000737:chemistry*; D008024:Ligands; D008163:Luminescent Measurements; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D009005:Monosaccharides / Q000737:chemistry*; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D012428:Ruthenium / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D004187:Disaccharides; D006001:Glycoconjugates; D037102:Lectins; D008024:Ligands; D009005:Monosaccharides; D009942:Organometallic Compounds; D015082:2,2'-Dipyridyl; D012428:Ruthenium; D007501:Iron