A Formylglycine-Peptide for the Site-Directed Identification of Phosphotyrosine-Mimetic Fragments.

Discovery of protein-binding fragments for precisely defined binding sites is an unmet challenge to date. Herein, formylglycine is investigated as a molecular probe for the sensitive detection of fragments binding to a spatially defined protein site . Formylglycine peptide 3 was derived from a phosphotyrosine-containing peptide substrate of protein tyrosine phosphatase PTP1B by replacing the phosphorylated amino acid with the reactive electrophile.

Direct Experimental Evidence for Halogen-Aryl π Interactions in Solution from Molecular Torsion Balances.

We dissected halogen-aryl π interactions experimentally using a bicyclic N-arylimide based molecular torsion balances system, which is based on the influence of the non-bonded interaction on the equilibria between folded and unfolded states. Through comparison of balances modulated by higher halogens with fluorine balances, we determined the magnitude of the halogen-aryl π interactions in our unimolecular systems to be larger than -5.0 kJ mol , which is comparable with the magnitude estimated in the biomolecular systems.

Live-cell MRI with xenon hyper-CEST biosensors targeted to metabolically labeled cell-surface glycans.

The targeting of metabolically labeled glycans with conventional MRI contrast agents has proved elusive. In this work, which further expands the utility of xenon Hyper-CEST biosensors in cell experiments, we present the first successful molecular imaging of such glycans using MRI. Xenon Hyper-CEST biosensors are a novel class of MRI contrast agents with very high sensitivity.

On the role of flexibility in protein-ligand interactions: the example of p53 tetramerization domain.

The recognition of protein surfaces by designed ligands has become an attractive approach in drug discovery. However, the variable nature and irregular behavior of protein surfaces defy this new area of research. The easy to understand "lock-and-key" model is far from being the ideal paradigm in biomolecular interactions and, hence, any new finding on how proteins and ligands behave in recognition events paves a step of the way.

Molecular recognition and self-assembly special feature: Calix[4]arene-based conical-shaped ligands for voltage-dependent potassium channels.

Potassium channels are among the core functional elements of life because they underpin essential cellular functions including excitability, homeostasis, and secretion. We present here a series of multivalent calix[4]arene ligands that bind to the surface of voltage-dependent potassium channels (K(v)1.x) in a reversible manner.

Solid-phase synthesis of chiral bicyclic guanidinium oligomers.

A simple solid-phase synthesis of thioether-linked chiral bicyclic guanidinium oligomers for cell internalization purposes has been developed. The approach is based on a Merrifield-like peptide synthesis on Rinkamide-p-methylbenzhydrylamine resin functionalized with Cys(methoxytrityl). A difunctionalized bicyclic guanidinium synthon, bearing both electrophile (O-mesyl) and protected nucleophile (S-methoxytrityl) group, is repeatedly grafted via a nucleophilic substitution.

Stability and structural recovery of the tetramerization domain of p53-R337H mutant induced by a designed templating ligand.

Protein p53 is a transcription factor crucial for cell cycle and genome integrity. It is able to induce both cell arrest when DNA is damaged and the expression of DNA repair machinery. When the damage is irreversible, it triggers apoptosis.

Binding to protein surfaces by supramolecular multivalent scaffolds.

Multivalency plays a pivotal role in biological recognition, particularly at protein-protein and protein-carbohydrate interaction sites. Scaffolds of diverse structure, flexibility, and valency are gaining increasing biomedical importance in the development of artificial multivalent ligands for these interfaces. Relevant examples range from small C(4) symmetric calix[4]arenes and porphyrin ligands, which may achieve nanomolar affinity for protein surfaces of pharmaceutical interest, to large-sized dendrimers that provide promising adherence-inhibition for toxins and other relevant lectins.

Highly efficient, nonpeptidic oligoguanidinium vectors that selectively internalize into mitochondria.

Oligoguanidinium-based cell delivery systems have gained broad interest in the drug delivery field since one decade ago. Thus, arginine-containing peptides as Tat or Antp, oligoarginine peptides, and derived peptoids have been described as shuttles for delivering nonpermeant drugs inside cancer cells. Herein we report a new family of tetraguanidinium cell penetrating vectors efficiently internalized in human tumor cells.

Expression of the aspartate/glutamate mitochondrial carriers aralar1 and citrin during development and in adult rat tissues.

Aralar1 and citrin are members of the subfamily of calcium-binding mitochondrial carriers and correspond to two isoforms of the mitochondrial aspartate/glutamate carrier (AGC). These proteins are activated by Ca2+ acting on the external side of the inner mitochondrial membrane. Although it is known that aralar1 is expressed mainly in skeletal muscle, heart and brain, whereas citrin is present in liver, kidney and heart, the precise tissue distribution of the two proteins in embryonic and adult tissues is largely unknown.