Thermodynamic Switch in Binding of Adhesion/Growth Regulatory Human Galectin-3 to Tumor-Associated TF Antigen (CD176) and MUC1 Glycopeptides.

A shift to short-chain glycans is an observed change in mucin-type O-glycosylation in premalignant and malignant epithelia. Given the evidence that human galectin-3 can interact with mucins and also weakly with free tumor-associated Thomsen-Friedenreich (TF) antigen (CD176), the study of its interaction with MUC1 (glyco)peptides is of biomedical relevance. Glycosylated MUC1 fragments that carry the TF antigen attached through either Thr or Ser side chains were synthesized using standard Fmoc-based automated solid-phase peptide chemistry.

Enhanced ratiometric fluorescent indicators for magnesium based on azoles of the heavier chalcogens.

Red-shifted fluorescent indicators for magnesium were developed by incorporation of sulfur or selenium in the azole moiety of 'fura' fluorophores. Single atom replacement in the acceptor of these ITC probes affords longer excitation and emission wavelengths as well as greater separation between excitation bands, valuable for ratiometric intracellular Mg(2+) imaging.

Formation of ternary complexes with MgATP: effects on the detection of Mg2+ in biological samples by bidentate fluorescent sensors.

Fluorescent indicators based on β-keto-acid bidentate coordination motifs display superior metal selectivity profiles compared to current o-aminophenol-N,N,O-triacetic acid (APTRA) based chelators for the study of biological magnesium. These low denticity chelators, however, may allow for the formation of ternary complexes with Mg(2+) and common ligands present in the cellular milieu. In this work, absorption, fluorescence, and NMR spectroscopy were employed to study the interaction of turn-on and ratiometric fluorescent indicators based on 4-oxo-4H-quinolizine-3-carboxylic acid with Mg(2+) and ATP, the most abundant chelator of biological magnesium, thus revealing the formation of ternary complexes under conditions relevant to fluorescence imaging.

Synthesis of side chain N,N'-diaminoalkylated derivatives of basic amino acids for application in solid-phase peptide synthesis.

Despite the enormous therapeutic potential, the clinical use of peptides has been limited by their poor bioavailability and low stability under physiological conditions. Hence, efforts have been undertaken to alter peptide structure in ways to improve their pharmacological properties. Inspired by the importance of basic amino acids in biological systems and the remarkable versatility displayed by lysine during the synthesis of complex peptide scaffolds, this chapter describes a simple procedure that enables rapid access to protected N,N'-diaminoalkylated basic amino acid building blocks suitable for standard solid-phase peptide synthesis.

Cyclic lipodepsipeptides: a new class of antibacterial agents in the battle against resistant bacteria.

In order to provide effective treatment options for infections caused by multidrug-resistant bacteria, innovative antibiotics are necessary, preferably with novel modes of action and/or belonging to novel classes of drugs. Naturally occurring cyclic lipodepsipeptides, which contain one or more ester bonds along with the amide bonds, have emerged as promising candidates for the development of new antibiotics. Some of these natural products are either already marketed or in advanced stages of clinical development.

Hydrogermylation of 5-ethynyluracil nucleosides: formation of 5-(2-germylvinyl)uracil and 5-(2-germylacetyl)uracil nucleosides.

A stereoselective radical-mediated hydrogermylation of the protected 5-ethynyluracil nucleosides with trialkyl-, triaryl,- or tris(trimethylsilyl)germanes gave (Z)-5-(2-germylvinyl)uridine, 2'-deoxyuridine, or ara-uridine as major products. Reaction of the β-triphenylgermyl vinyl radical intermediate with oxygen and fragmentation of the resulting peroxyradical provided also 5-[2-(triphenylgermyl)acetyl]pyrimidine nucleosides in low to moderate yields. Thermal isomerization of the latter in MeOH occurred via a four-centered activated complex, and subsequent hydrolysis of the resulting O-germyl substituted enol yielded 5-acetyluracil nucleosides in quantitative yield.

Solid-phase synthesis of fusaricidin/LI-F class of cyclic lipopeptides: Guanidinylation of resin-bound peptidyl amines.

Fusaricidins/LI-Fs and related cyclic lipopeptides represent an interesting new class of antibacterial peptides with the potential to meet the challenge of antibiotic resistance in bacteria. Our previous study (Bionda et al. ChemMedChem 2012, 7, 871-882) revealed the significance of the guanidinium group located at the termini of the lipidic tails of these cyclic lipopeptides for their antibacterial activities.

Direct access to side chain N,N'-diaminoalkylated derivatives of basic amino acids suitable for solid-phase peptide synthesis.

A simple and efficient one-pot procedure that enables rapid access to orthogonally protected N,N'-diaminoalkylated basic amino acid building blocks fully compatible with standard Boc and Fmoc solid-phase peptide synthesis is reported. Described synthetic approach includes double reductive alkylation of N (α)-protected diamino acids with N-protected amino aldehydes in the presence of sodium cyanoborohydride. This approach allows preparation of symmetrical, as well as unsymmetrical, basic amino acid derivatives with branched side-chains that can be further modified, enhancing their synthetic utility.

Fluoride-promoted cross-coupling of chloro(mono-, di-, or triphenyl)germanes with aryl halides in "moist" toluene. Multiple transfer of the phenyl group from organogermane substrates and comparison of the coupling efficiencies of chloro(phenyl)germanes with their corresponding stannane and silane counterparts.

The trichlorophenyl-, dichlorodiphenyl-, and chlorotriphenylgermanes undergo Pd-catalyzed cross-couplings with aryl bromides and iodides in the presence of tetrabutylammonium fluoride in toluene with addition of the measured amount of water. One chloride ligand on the Ge center allows efficient activation by fluoride to promote transfer of one, two, or three phenyl groups from the organogermanes. The corresponding chlorophenylstannanes were found to be more reactive than chlorophenylsilanes, which in turn were more effective than chlorophenylgermanes.

Arylchlorogermanes/TBAF/"moist" toluene: a promising combination for Pd-catalyzed Germyl-Stille cross-coupling.

The trichlorophenyl,- dichlorodiphenyl,- and chlorotriphenylgermanes undergo Pd-catalyzed cross-couplings with aryl bromides and iodides in the presence of TBAF in toluene with addition of the measured amount of water. One chloride ligand on the Ge center allows efficient activation by fluoride to promote transfer of one, two, or three phenyl groups from the organogermane precursors.

Vinyl Tris(trimethylsilyl)silanes: Substrates for Hiyama Coupling.

The oxidative treatment of vinyl tris(trimethylsilyl)silanes with hydrogen peroxide in aqueous sodium hydroxide in tetrahydrofuran generates reactive silanol or siloxane species that undergo Pd-catalyzed cross-couplings with aryl, heterocyclic and alkenyl halides in the presence of Pd(PPh(3))(4) and tetrabutylammonium fluoride. Hydrogen peroxide and base are necessary for the coupling to occur while activation of the silanes with fluoride is not required. The conjugated and unconjugated tris(trimethylsilyl)silanes serve as good cross-coupling substrates.