Diamino-Pentane [BSA]

Hydrophilic networks based on functionalized hyaluronic acid and on partially acetylated chitosan, respectively, have been obtained. In the case of hyaluronic acid (HA), primary amino functionalities have been introduced along the polysaccharide chains. The ensuing derivatives, i.e., HA-lysine (HA-K), HA-diamino pentane (HA-DAP), and HA-glycine-lysine (HA-GK), have been characterized by high field NMR spectroscopy. NMR 2D-DOSY experiments have allowed us to optimize the purification procedure. Chitosan was made soluble in water by partial acetylation. Cross-linking reactions have been performed using glutaraldehyde. The obtained networks have been qualitatively characterized by means of C-13 CP-MAS NMR technique. The hydrogels have been characterized also in terms of water uptake.

The water solubility of a natural product-inspired octadentate hydroxamic acid chelator designed to coordinate Zr(IV)-89 has been improved by using a combined microbiological-chemical approach to engineer four ether oxygen atoms into the main-chain region of a methylene-containing analogue. First, an analogue of the trimeric hydroxamic acid desferrioxamine B (DFOB) that contained three main-chain ether oxygen atoms (DFOB-O-3) was generated from cultures of the native DFOB-producer Streptomyces pilosus supplemented with oxybis(ethanamine) (OBEA), which competed against the native 1,5-diamino-pentane (DP) substrate during DFOB assembly. This precursor-directed biosynthesis (PDB) approach generated a suite of DFOB analogues containing one (DFOB-O-1), two (DFOB-O-2) or three (DFOB-O-3) ether oxygen atoms, with the latter produced as the major species. Log P measurements showed DFOB-O-3 was about 45 times more water soluble than DFOB. Second, a peptide coupling chain-extension reaction between DFOB-O-3 and the synthetic ether-containing endo-hydroxamic acid monomer 4-((2-(2-aminoethoxy) ethyl)(hydroxy) amino)-4-oxobutanoic acid (PBH-O-1) gave the water soluble tetrameric hydroxamic acid DFOB-O-3-PBH-O-1 as an isostere of sparingly water soluble DFOB-PBH. The complex between DFOB-O-3-PBH-O-1 and Zr-nat(IV), examined as a surrogate measure of the radiolabelling procedure, analysed by LC-MS as the protonated adduct ([M + H]+, m/z(obs) = 855.2; m/z(calc) = 855.3), with supporting HRMS data. The use of a microbiological system to generate a water-soluble analogue of a natural product for downstream semi-synthetic chemistry is an attractive pathway for developing new drugs and imaging agents. The improved water solubility of DFOB-O-3-PBH-O-1 could facilitate the synthesis and purification of downstream products, as part of the ongoing development of ligands optimised for Zr(IV)-89 immunological PET imaging.