Tuning a modular system - synthesis and characterisation of a boron-rich s-triazine-based carboxylic acid and amine bearing a galactopyranosyl moiety.

Introduction of a bis(isopropylidene)-protected galactopyranosyl moiety in s-triazine-based boron-rich carboxylic acids and amines results in soluble and suitable coupling partners for tumour-selective biomolecules with applications as selective agents for boron neutron capture therapy (BNCT). Bearing either a carboxylic acid or primary amine as a functional group, these compounds are highly versatile and thus largely extend the possible coupling strategies with suitable biomolecules. Modification of the gastrin-releasing peptide receptor (GRPR) selective agonist [d-Phe, β-Ala, Ala, Nle]Bn(6-14) with the carboxylic acid derivative yielded a bioconjugate with an optimal receptor activation and internalisation profile.

Enlargement of a Modular System-Synthesis and Characterization of an -Triazine-Based Carboxylic Acid Ester Bearing a Galactopyranosyl Moiety and an Enormous Boron Load.

The amount of boron accumulated in tumor tissue plays an important role regarding the success of the boron neutron capture therapy (BNCT). In this article, we report a modular system, combining readily available starting materials, like glycine, 1,3,5-triazine and the well-known 9-mercapto-1,7-dicarba--dodecaborane(12), as well as α-d-galactopyranose for increased hydrophilicity, with a novel boron-rich tris--carboranyl thiol.

Modular triazine-based carborane-containing carboxylic acids - synthesis and characterisation of potential boron neutron capture therapy agents made of readily accessible building blocks.

Based on a modular combination of s-triazine, the well-known 9-mercapto-1,7-dicarba-closo-dodecaborane(12) and commercially available carboxylic acids, namely thioglycolic acid, glycine, and N-Boc-l-lysine, several carboxylic acid derivatives were synthesised and fully characterised. The thioglycolic acid derivative was introduced into a peptide hormone by solid phase peptide synthesis. High activity and selective internalisation into peptide receptor-expressing cells was observed.

Adrenomedullin disulfide bond mimetics uncover structural requirements for AM receptor activation.

Adrenomedullin (ADM) is a vasoactive peptide hormone of 52 amino acids and belongs to the calcitonin peptide superfamily. Its vasodilative effects are mediated by the interaction with the calcitonin receptor-like receptor (CLR), a class B G protein-coupled receptor (GPCR), associated with the receptor activity modifying protein 2 (RAMP2) and functionally described as AM-1 receptor (AM R). A disulfide-bonded ring structure consisting of six amino acids between Cys and Cys has been shown to be a key motif for receptor activation.

A stable meta-carborane enables the generation of boron-rich peptide agonists targeting the ghrelin receptor.

Boron neutron capture therapy (BNCT) is a binary cancer therapy, which combines the biochemical targeting of a boron-containing drug with the regional localization of radiation treatment. Although the concept of BNCT has been known for decades, the selective delivery of boron into tumor cells remains challenging. G protein-coupled receptors that are overexpressed on cancer cells in combination with peptidic ligands can be potentially used as shuttle system for a tumor-directed boron uptake.