Acetohydroxamic Acid

Hyaluronic acid (HA) self-healing hydrogels commonly suffer from an imbalance between mechanical properties and self-healing efficiency. To address this issue, we introduce carboxymethyl-β-cyclodextrin (β-CD) into the HA hydrogel system, which provides multiple crosslinking sites via β-CD's cyclic structure to improve its self-healing capability. The β-cyclodextrin/hyaluronic acid (ACD) hydrogels were prepared through dynamic acylhydrazone bond formation between aldehyde-modified HA (AHA) and hydrazide-modified carboxymethyl-β-cyclodextrin (β-CDD). Compared to aldehyde-modified HA/3,3'-dithiobis (propionyl hydrazide) (AHA/DTP, AD) hydrogels (~0.17 MPa), ACD hydrogels exhibited enhanced compressive strength of ~0.29 MPa, which was attributed to multiple interactions, such as dynamic covalent acylhydrazone bonds, hydrogen bonds, and physical filling. Furthermore, ACD hydrogels achieved 100 % healing efficiency in Young's modulus within 10 min, significantly higher than AD hydrogel (80 %) due to synergistic effects of dynamic covalent bonds, including acylhydrazone and disulfide bonds and hydrogen bonds. This hydrogel holds potential for various biomedical applications.

α-Hydroxy acids (AHAs) and polyhydroxy acids (PHAs) are of key importance in organic synthesis and find numerous applications in various industries. However, the stereoselective synthesis of these compounds, whether enzymatic or chemical, remains a major challenge. In this study, we uncover a previously uncharacterized family of lactate racemase homologs (LarAHs) within the LarA superfamily and show their ability to catalyze the interconversion of AHA and PHA stereoisomers. Through systematic biochemical characterization, we investigated the substrate specificity, catalytic properties, and structural modelling of four representative LarAHs from this novel family. Our findings demonstrate that these enzymes act as broad-spectrum hydroxy acid isomerases (BSHIs) and exhibit racemase activity on up to 15 structurally diverse AHAs (including aliphatic, aromatic, and polycarboxylic AHAs), and C2-epimerase activity on up to 24 distinct PHAs (including aldonic acids, uronic acids, aldaric acids, and other sugar-derived acids). Notably, 20 of the sugar acid C2-epimerization reactions identified were previously unreported. Structural analysis revealed that BSHIs possess an original C-terminal fold that forms a substrate-binding site adapted for bulky substrates, with considerable active-site flexibility likely contributing to their broad substrate specificity. Collectively, these findings suggest the biotechnological potential of BSHIs for stereoselective interconversion of valuable AHA and PHA stereoisomers.