Altering the strength of lectin binding interactions and controlling the amount of lectin clustering using mannose/hydroxyl-functionalized dendrimers.

Protein-carbohydrate interactions play a critical role in many biological recognition events. Multivalent therapeutic agents that utilize protein-carbohydrate interactions have proven difficult to design, primarily because the fundamental requirements of protein-carbohydrate interactions are not well understood. Here, we report a systematic study of the effect on lectin binding of varying the loading of mannose surface residues on generations three through six PAMAM dendrimers. The degree of mannose functionalization was controlled by stoichiometric addition, and dendrimers were characterized using NMR and MALDI-TOF MS. Hemagglutination assays and quantitative precipitation assays were performed to determine the relative activity of the dendrimers. Using the mannose/hydroxyl-functionalized dendrimers reported here, we could systematically control both the degree of lectin clustering and the overall activity of the lectin with the dendrimer.

The lectin-binding properties of six generations of mannose-functionalized dendrimers.

[structure: see text] First- through sixth-generation PAMAM dendrimers have been functionalized with mannose residues. Characterization with MALDI-TOF MS and (1)H NMR is reported. Different binding enhancements consistent with monovalent interaction, glycoside clustering, and multivalent binding are observed for different generations of dendrimers.

19F NMR and Structural Evidence for Spin-State Modulation of Six-Coordinate Cobalt(II) in a Weak Field Porphyrin Ligand(1).

The syntheses and characterization of [2,3,7,8,12,13,17,18-octafluoro-5,10,15,20-tetraphenylporphinato]cobalt, Co(F(8)TPP), and [2,3,7,8,12,13,17,18-octafluoro-5,10,15,20-tetrakis(pentafluorophenyl)porphinato]cobalt, Co(F(28)TPP), are reported. Co(F(28)TPP).2tol (tol = toluene) crystallizes in the monoclinic space group C2/c-C(h)() (No. 15) with a = 22.1616(5) Å, b = 12.0274(3) Å, c = 19.9159(2) Å, beta = 110.645(1) degrees, V = 4967.6(2) Å(3), and Z = 4 {d(calcd) = 1.818 g/cm(3); &mgr;(a)(Mo Kalpha) = 0.50 mm(-)(1)}, and Co(F(28)TPP).2THF crystallizes in the triclinic space group P&onemacr; (No. 2) with a = 11.0691(1) Å, b = 12.0451(1) Å, c = 12.9558(2) Å, alpha = 62.531(1) degrees, beta = 69.544(1) degrees, gamma = 76.181(1) degrees, V = 1429.71(3) Å(3) and Z = 1 {d(calcd) = 1.700 g/cm(3); &mgr;(a)(Mo Kalpha) = 0.45 mm(-)(1)}. A comparison of the X-ray crystal structure data from Co(F(28)TPP).2tol and Co(F(28)TPP).2THF indicates that the porphyrin core expands dramatically (0.08 Å) in the six-coordinate complex. Optical and (19)F NMR spectroscopic studies of Co(F(28)TPP) in the presence of added ligand demonstrate that spin-state modulation of the six-coordinate Co(II) center is facile. Partial population of the (4)E(g) state is accessed upon coordination of the cobalt center with THF sigma-donor ligands, while six-coordinate complexes with 1-methylimidazole result in complete conversion to the high spin state, as evinced by 280 ppm downfield chemical shifts for the beta-fluorine resonances in the (19)F NMR spectrum. Co(F(28)TPP) is the first example of a porphyrin which supports a high-spin cobalt ion.