Artificial Metalloglycoclusters:  Compact Saccharide Shell to Induce High Lectin Affinity as Well as Strong Luminescence

• Published in: Bioconjugate chemistry Vol. 14; no. 4; pp. 728 - 737
• Main Authors: Hasegawa, Teruaki, Yonemura, Takahiro, Matsuura, Kazunori, Kobayashi, Kazukiyo
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 16-07-2003
• Subjects: 2,2'-Dipyridyl - analogs & derivatives; 2,2'-Dipyridyl - chemical synthesis; 2,2'-Dipyridyl - chemistry; Binding Sites; Circular Dichroism; Disaccharides - chemistry; Glycoconjugates - chemistry; Iron - chemistry; Lectins - chemistry; Ligands; Luminescent Measurements; Magnetic Resonance Spectroscopy; Models, Chemical; Models, Molecular; Molecular Structure; Monosaccharides - chemistry; Organometallic Compounds - chemical synthesis; Organometallic Compounds - chemistry; Ruthenium - chemistry; Stereoisomerism; Structure-Activity Relationship
• ISSN: 1043-1802; 1520-4812
• DOI: 10.1021/bc020026a

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 α-manno clusters exhibited excellent affinities (ICmin = 9.0 × 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 (ΔH° = −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 (Φem = 0.15), and their luminescence intensities were changed (∼40%) upon binding to the specific lectins. The ruthenium glycoclusters can be a suitable sensory system for saccharide-binding phenomena.