Targeting multidrug resistant Staphylococcus aureus with cationic chlorpromazine-peptide conjugates.

Antimicrobial resistance is a serious public health risk. Its severity is fueled on an unprecedented scale, necessitating the demand for novel antimicrobial scaffolds aimed at novel targets. Herein, we present cationic chlorpromazine peptide conjugates that are rationally intended to targetmultidrug-resistant (MDR) bacteria. The most potent compound, CPWL, of all the conjugates evaluated, showed promising antibacterial activity against clinical, MDR S. aureus, with no cytotoxicity. The molecular docking experiments confirmed that CPWL possessed a very high affinity for S. aureus enoyl reductase (saFabI). Furthermore, CPWL antibacterial action against saFabI was further corroborated by MD simulation studies. Thus, our findings highlight cationic chlorpromazine as a promising scaffold for the development of saFabI inhibitors to target severe staphylococcal infections.

Anionic diketopiperazine induces osteogenic differentiation and supports osteogenesis in a 3D cryogel microenvironment.

Bioactive molecules that enhance or induce osteogenic potential of bone precursor cells have shown vital roles in bone tissue engineering. Herein, we report the design and synthesis of a novel diketopiperazine (DT) that induces osteoblastic differentiation of pre-osteoblasts and bone-marrow-derived stem cells in vitro and enhances the osteogenic potential of cryogel matrix. Such functional diketopiperazines can serve as potential scaffolds for bone healing and regeneration.

Spin coating mediated morphology modulation in self assembly of peptides.

Controlling the morphology and nanostructure of self-assembled peptide molecules is of fundamental importance to chemistry and material science due to their bioactivity in both in vivo and in vitro settings, ability to act as templates for conjugating bio-recognition elements, hybrid supramolecular assembly, possible detection and treatment of diseases and so on. In this article, we show that spin coating, a widely utilized method for obtaining ultra-thin polymer films, has been utilised to modulate the self-assembly of peptide molecules, which has traditionally been achieved by chemical functionalisation of the molecules. With the specific example of diphenylalanine-based peptide molecules, we show that a variety of self-assembled architectures such as long fibrils, short fibrils, globules, nanodots, and so on, spanning over large areas can be obtained by simultaneously varying the spinning speed (RPM) and the solution concentration (Cp) during spin coating. We correlate the variation in morphology to a transition from spin dewetting at very low Cp (or high RPM) to the formation of continuous films at high Cp (or low RPM) during the initial stage of spin coating. We further show the generality of the approach by achieving distinct self-assembled morphologies with diphenylalanine analogues with different C-terminal and N-terminal groups by modulation of spin coating parameters, though the exact morphology obtained under identical coating conditions depends on the chemical nature of the peptide molecules. The work opens up a new possible route for creating complex peptide assemblies on demand by simultaneous control of molecular functionalisation and spin coating parameters vis - a - vis the applied centrifugal force.

Peptide-Based Scaffold for Nitric Oxide Induced Differentiation of Neuroblastoma Cells.

Nitric oxide is a gaseous messenger involved in neuronal differentiation, development and synaptogenesis, in addition to many other physiological functions. Therefore, it is imperative to maintain an optimal nitric oxide concentration to ensure its biochemical function. A sustained nitric oxide releasing scaffold, which supports neuronal cell differentiation, as determined by morphometric analysis of neurite outgrowth, is described. Moreover, the effect of nitric oxide on the neuroblastoma cell line was also confirmed by immunofluorescent analysis of neuronal nuclear protein (NeuN), specific neuronal marker and neurofilament (NF) protein, which revealed a significant increase in their expression levels, in comparison with undifferentiated cells.