Rapid Probing of Biological Surfaces with a Sparse-Matrix Peptide Library

Finding unique peptides to target specific biological surfaces is crucial to basic research and technology development, though methods based on biological arrays or large libraries limit the speed and ease with which these necessary compounds can be found. We reasoned that because biological surfaces, such as cell surfaces, mineralized tissues, and various extracellular matrices have unique molecular compositions, they present unique physicochemical signatures to the surrounding medium which could be probed by peptides with appropriately corresponding physicochemical properties. To test this hypothesis, a naïve pilot library of 36 peptides, varying in their hydrophobicity and charge, was arranged in a two-dimensional matrix and screened against various biological surfaces. While the number of peptides in the matrix library was very small, we obtained “hits” against all biological surfaces probed. Sequence refinement of the “hits” led to peptides with markedly higher specificity and binding activity against screened biological surfaces. Genetic studies revealed that peptide binding to bacteria was mediated, at least in some cases, by specific cell-surface molecules, while examination of human tooth sections showed that this method can be used to derive peptides with highly specific binding to human tissue

Spiro Iminosugars: Structural Diversity and Synthetic Strategies

International audienceFrom their discovery in the late 1960s, iminosugars have undergone an expansion from an area of science limited to a few researchers to a field that now attracts the interest of members of the whole synthetic organic chemistry community. Indeed, many tasks concern structural modifications of standard iminosugars in order to improve their biological and pharmacological properties. In this way, the introduction of an adjoining spirocycle afforded unprecedented polyhydroxy-azaspiranes, the structures and syntheses of which are presented in this chapter. Special attention is paid to the key steps involved in the generation of the pivotal quaternary spiro atom