A mechanoresponsive heterochiral hydrogelator as a potential matrix metalloproteinase-2 inhibitor: unravelling its anti-inflammatory efficacy and .

Inflammations are innate and adaptive immune responses that get instigated in reciprocation to infection. However, if left unchecked, they pose a formidable challenge in clinical settings. In search of user-friendly solutions, our work delineated a rational combinatorial strategy, harnessing chiral orchestration in a triphenylalanine fragment and appending it to δ-amino valeric acid at the N-terminus (hydrogelators I-VIII) such that a potential matrix metalloproteinase-2 (MMP2) inhibitor could be fished out from the design. Our rigorous investigations revealed that from a pool of eight constructs, hydrogelator VIII, with a DLL configuration at the triphenylalanines, displayed excellent MMP2 inhibitory activities , which was further supported by molecular modelling studies. Besides, the β-sheet structured scaffold not only showed substantial antibacterial efficacy against the Gram-positive pathogens , , and but also exhibited proteolytic stability and biocompatibility towards mammalian cells. Furthermore, the scaffold possessed high mechanical strength at physiological pH and mechanical stress-triggered gel-sol-gel transition properties. Finally, the efficacy was evaluated using an air pouch model of acute inflammation in albino mice that certified hydrogelator VIII as a promising anti-inflammatory therapeutic to pave the path for future healthcare management.