Hsp90 is a molecular chaperone that plays a pivotal role in the cell life cycle. ATP‐regulated internal dynamics are critical to Hsp90 function and we recently demonstrated that these dynamics can be modulated in an allosteric fashion; the protein C‐terminal domain (CTD) can be effectively targeted with a family of 2‐phenyl‐benzofuran derivatives. Here we describe the expansion of the initial library, reporting 28 new derivatives that explore the chemical space at opposite ends of the benzofuran scaffold. Interactions of the compounds with a full‐length protein homolog were explored by Saturation Transfer Difference (STD) NMR spectroscopy. In this context we also report the interaction epitope of Novobiocin, a known CTD inhibitor.

Teichoic acids (TAs) are key components of the Gram‐positive bacterial cell wall that are composed of alditol phosphate repeating units, decorated with alanine or carbohydrate appendages. Because of their microhetereogeneity, pure well‐defined TAs for biological or immunological evaluation cannot be obtained from natural sources. We present here a streamlined automated solid‐phase synthesis approach for the rapid generation of well‐defined glycosylated, glycerol‐based TA oligomers. Building on the use of a “universal” linker system and fluorous tag purification strategy, a library of glycerolphosphate pentadecamers, decorated with various carbohydrate appendages, is generated. These are used to create a structurally diverse TA‐microarray, which is used to reveal, for the first time, the binding preferences of anti‐LTA (lipoteichoic acids) antibodies at the molecular level.

Glycerol stereochemistry is key for teichoic acid synthesis and antibodies binding.

No abstract

Glycerol phosphate (GroP)-based teichoic acids (TAs) are antigenic cell-wall components found in both enterococcus and staphylococcus species. Their immunogenicity has been explored using both native and synthetic structures, but no details have yet been reported on the structural basis of their interaction with antibodies. This work represents the first case study in which a monoclonal antibody, generated against a synthetic TA, was developed and employed for molecular-level binding analysis using TA microarrays, ELISA, SPR-analyses, and STD-NMR spectroscopy. Our findings show that the number and the chirality of the GroP residues are crucial for interaction and that the sugar appendage contributes to the presentation of the backbone to the binding site of the antibody.