A quantitative approach of the interaction between metal triflates and organic ligands using electrospray mass spectrometry.

The interaction between two Lewis "superacid" catalysts Zn(OTf)(2) and In(OTf)(3) and series of amide and phosphate ligands is quantitatively characterized by electrospray ionization mass spectrometry (ESI-MS). A specific feature of the ESI-MS spectra of the mixture of metal triflates and Lewis bases is the formation of ionic adducts resulting from the displacement of one triflate anion by two neutral ligands. A ligand competition model is developed, which describes the relative intensities of the ionic adducts as a function of relative ligand concentrations.

Screening multicomponent reactions for X-linked inhibitor of apoptosis-baculoviral inhibitor of apoptosis protein repeats domain binder.

We report a second example of a general reaction screening approach to discover low molecular weight inhibitors of protein protein interactions. On the basis of the known pharmacophore model of SMAC mimetics, we predicted several inhibitors based on four different multicomponent reactions. The predicted inhibitors were subsequently synthesized, tested, and found to bind to the antiapoptotic protein X-linked inhibitor of apoptosis protein (XIAP) and showed cellular activity.

Relative basicities toward metal triflates Lewis acids by electrospray mass spectrometry.

The relative Lewis basicity of a series of phosphoryl compounds toward cations M(n+)(OTf)(n-1) derived from triflate salts, M(OTf)(n), is ranked using electrospray mass spectrometry according to competitive adduct formation.

Mass spectrometric characterization of metal triflates and triflimides (Lewis superacid catalysts) by electrospray ionization and tandem mass spectrometry.

Trifluoromethylsulfonate (triflate) and bis(trifluoromethylsulfonyl)imide (triflimide) salts, well-known Lewis acid catalysts, present some difficulty in their characterization. By using nitromethane as the solvent, useful electrospray mass spectra in positive and negative ion mode were obtained for salts of metals in oxidation states +2 and +3. In positive mode, addition of a strong Lewis base (triphenylphosphine oxide, TPPO), capable of displacing a triflate (TfO(-)) or a triflimide (Tf(2)N(-)) anion, is necessary for obtaining useful spectra.

Multicomponent synthesis of dihydrobenzoxazepinones, bearing four diversity points, as potential α-helix mimics.

A very short convergent synthesis of dihydrobenzoxazepinones, bearing four diverse diversity points, based on coupling the Ugi reaction with a Mitsunobu cyclization, was developed. These compounds are potential α-helix mimics, where three of the four appendages are expected to imitate the residues in i, i + 4 and i + 7 positions. A library of 22 compounds bearing lipophilic substituents, designed to interact with the hydrophobic cleft of anti-apoptotic protein Bcl-xL, was synthesized.

A novel Bim-BH3-derived Bcl-XL inhibitor: biochemical characterization, in vitro, in vivo and ex-vivo anti-leukemic activity.

BH3-only members of the Bcl-2 family exert a fundamental role in apoptosis induction. This work focuses on the development of a novel peptidic molecule based on the BH3 domain of Bim. The antiapoptotic molecule Bcl-X(L), involved in cancer development/progression and tumour resistance to cytotoxic drugs, is a target for Bim.