Asymmetric structure of cis-[N-(9-anthracenylmethyl)-1,2-ethanediamine]dipyridineplatinum(II) dinitrate.

Platinum antitumour agents, containing aromatic rings, which are used for targeting DNA in effective therapies for the treatment of cancer. We have synthesized the title metallocomplex with an aromatic ligand and determined its crystal structure. In many cases, complexes of platinum and other metals have a symmetrical structure.

Complexes of myo-Inositol-Hexakisphosphate (IP6) with Zinc or Lanthanum for the Decorporation of Radiocesium.

Radioactive nuclides leak into the surrounding environment after nuclear power plant disasters, such as the Chernobyl accident and the Fukushima Daiichi Nuclear Power Plant disaster. Cesium-137 (Cs) (t=30.1 year), a water-soluble radionuclide with a long physical half-life, contaminates aquatic ecosystems and food products.

Water-soluble metalloporphyrinates with excellent photo-induced anticancer activity resulting from high tumor accumulation.

To develop a water-soluble and tumor-targeted photosensitizer for photodynamic therapy (PDT), a porphyrin framework containing the metal ion gallium(III) was combined with platinum(II)-based groups to produce two new pentacationic metalloporphyrinates, Ga-4cisPtTPyP (5,10,15,20-tetrakis{cis-diammine-chloro-platinum(II)}(4-pyridyl)-porphyrinato gallium(III) hydroxide tetranitrate) and Ga-4transPtTPyP (5,10,15,20-tetrakis{trans-diammine-chloro-platinum(II)} (4-pyridyl)-porphyrinato gallium(III) hydroxide tetranitrate). Both complexes exhibited high singlet oxygen quantum yields (Φ) and remarkable photocytotoxicity with appreciable phototoxic indexes (PIs). In particular, Ga-4cisPtTPyP showed a low IC value (Colon 26: 0.

Development of novel radiogallium-labeled bone imaging agents using oligo-aspartic acid peptides as carriers.

(68)Ga (T 1/2 = 68 min, a generator-produced nuclide) has great potential as a radionuclide for clinical positron emission tomography (PET). Because poly-glutamic and poly-aspartic acids have high affinity for hydroxyapatite, to develop new bone targeting (68)Ga-labeled bone imaging agents for PET, we used 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) as a chelating site and conjugated aspartic acid peptides of varying lengths. Subsequently, we compared Ga complexes, Ga-DOTA-(Asp)n (n = 2, 5, 8, 11, or 14) with easy-to-handle (67)Ga, with the previously described (67)Ga-DOTA complex conjugated bisphosphonate, (67)Ga-DOTA-Bn-SCN-HBP.

Extramembrane control of ion channel peptide assemblies, using alamethicin as an example.

Ion channels allow the influx and efflux of specific ions through a plasma membrane. Many ion channels can sense, for example, the membrane potential (the voltage gaps between the inside and the outside of the membrane), specific ligands such as neurotransmitters, and mechanical tension within the membrane. They modulate cell function in response to these stimuli.

Development and evaluation of a radiobromine-labeled sigma ligand for tumor imaging.

Introduction: Sigma receptors are appropriate targets for tumor imaging because they are highly expressed in a variety of human tumors. Previously, we synthesized a vesamicol analog, (+)-2-[4-(4-iodophenyl)piperidino]cyclohexanol ((+)-pIV), with high affinity for sigma receptors, and prepared radioiodinated (+)-pIV. In this study, to develop a radiobromine-labeled vesamicol analog as a sigma receptor imaging agent for PET, nonradioactive and radiobromine-labeled (+)-2-[4-(4-bromophenyl)piperidino]cyclohexanol ((+)-pBrV) was prepared and evaluated in vitro and in vivo.

Development and evaluation of a novel radioiodinated vesamicol analog as a sigma receptor imaging agent.

Background: Sigma receptors are highly expressed in human tumors and should be appropriate targets for developing tumor imaging agents. Previously, we synthesized a vesamicol analog, (+)-2-[4-(4-iodophenyl)piperidino]cyclohexanol ((+)-pIV), with a high affinity for sigma receptors and prepared radioiodinated (+)-pIV. As a result, (+)-[125I]pIV showed high tumor uptake in biodistribution experiments.

Preparation and evaluation of a radiogallium complex-conjugated bisphosphonate as a bone scintigraphy agent.

Introduction: (68)Ga is a radionuclide of great interest as a positron emitter for positron emission tomography (PET). To develop a new bone-imaging agent with radiogallium, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was chosen as a chelating site and Ga-DOTA complex-conjugated bisphosphonate, which has a high affinity for bone, was prepared and evaluated. Although we are interested in developing (68)Ga-labeled bone imaging agents for PET, in these initial studies (67)Ga was used because of its longer half-life.

Role of calcineurin signaling in membrane potential-regulated maturation of cerebellar granule cells.

At the early postnatal period, cerebellar granule cells proliferate, differentiate, migrate, and finally form refined synaptic connections with mossy fibers. During this period, the resting membrane potential of immature granule cells is relatively depolarized, but it becomes hyperpolarized in mature cells. This investigation was conducted to examine the role of this alteration in membrane potential and its downstream signaling mechanism in development and maturation of granule cells.

Transmission of extramembrane conformational change into current: construction of metal-gated ion channel.

Interaction with Fe(III) induces the reversible conformational switch of the extramembrane segment in the artificial receptor channel, which is transmitted into membranes as an increase in channel current (ion flux).

Control of peptide structure and recognition by Fe(III)-induced helix destabilization.

Helical peptide segments that change their conformation due to external stimuli have often been employed in peptide-based molecular devices and materials. Using helices containing a pair of the iminodiacetic acid derivatives of lysine (Ida), we show that metal-induced helix destabilization is a promising approach to functional switching, especially for helices that are intrinsically stable. By i and i + 2 positioning of the Ida residues in a 17-residue model peptide, a significant decrease in the helical content was observed by the addition of Fe(III), whereas Fe(II) had no influence on the stability of the helix.

Total synthesis of artificial zinc-finger proteins: Problems and perspectives.

The total synthesis of a peptide segment corresponding to the DNA-binding segment of Sp1 (positions 532-623) using a native chemical ligation approach is described. The folding of the synthetic segment in the presence of Zn(II) gave a zinc-coordinated protein. The dissociation constant (K(D)) for the DNA binding of the resulting protein, determined by a gel mobility shift assay, was 130 nM, almost nine times higher than that of the genetically prepared protein.

Gramicidin-based channel systems for the detection of protein-ligand interaction.

To detect protein-ligand interaction a gramicidin-based sensor was developed. Biotin was tagged to the C-terminus of gramicidin (Gram-bio 1). The biotin-moiety, which faces the electrolyte, gave little effect on single-channel conductance.

Alpha,alpha-disubstituted glycines bearing a large hydrocarbon ring: peptide self-assembly through hydrophobic recognition.

A method was developed for synthesizing alpha,alpha-disubstituted glycine residues bearing a large (more than 15-membered) hydrophobic ring. The ring-closing metathesis reactions of the dialkenylated malonate precursors proceed efficiently, particularly when long methylene chains tether both terminal olefin groups. Surprisingly, the amino groups of these alpha,alpha-disubstituted glycines are inert to conventional protective reactions (e.

Detection of protein-ligand interaction on the membranes using C-terminus biotin-tagged alamethicin.

C-terminal biotin-tagged alamethicin, which has several alpha-aminoisobutyric acid (Aib) residues in its sequence, was synthesized by the preparation of the protected peptide segment using the 2-chlorotrityl resin, followed by conjugation with biotin hydrazide. Suppression of the channel current of the biotin-tagged alamethicin by the addition of streptavidin to the electrolyte was monitorable in real time using the planar lipid-bilayer method. The system was also applicable to the detection of interaction of the biotin-tagged alamethicin with the anti-biotin antibody.

Kinetic analysis of the interaction between vitronectin and the urokinase receptor.

Although the urokinase receptor (uPAR) binds to vitronectin (VN) and promotes the adhesion of cells to this matrix protein, the biochemical details of this interaction remain unclear. VN variants were employed in BIAcore experiments to examine the uPAR-VN interaction in detail and to compare it to the interaction of VN with other ligands. Heparin and plasminogen bound to VN fragments containing the heparin-binding domain, indicating that this domain was functionally active in the recombinant peptides.