Gram-negative bacteria contain a double membrane which serves for both protection and for providing nutrients for viability. The outermost of these membranes is called the outer membrane (OM), and it contains a host of fully integrated membrane proteins which serve essential functions for the cell, including nutrient uptake, cell adhesion, cell signalling and waste export. For pathogenic strains, many of these outer membrane proteins (OMPs) also serve as virulence factors for nutrient scavenging and evasion of host defence mechanisms. OMPs are unique membrane proteins in that they have a β-barrel fold and can range in size from 8 to 26 strands, yet can still serve many different functions for the cell. Despite their essential roles in cell survival and virulence, the exact mechanism for the biogenesis of these OMPs into the OM has remained largely unknown. However, the past decade has witnessed significant progress towards unravelling the pathways and mechanisms necessary for moulding a nascent polypeptide into a functional OMP within the OM. Here, we will review some of these recent discoveries that have advanced our understanding of the biogenesis of OMPs in Gram-negative bacteria, starting with synthesis in the cytoplasm to folding and insertion into the OM.

Suramin inhibits STING pathway via the inhibition of cGAS enzymatic activity. Suramin or analogs thereof that displace DNA from cGAS could be used as anti-inflammatory drugs.

HSD1169 or an analog could become a therapeutic agent for AML containing drug-resistant FLT3-ITD.

Histone modification, a post-translational modification of histones and involving various covalent tags, such as methyl, phosphate and acetate groups, affects gene expression and hence modulates various cellular events, including growth and proliferation. Consequently histone-modifying proteins have become targets for the development of anticancer agents. Thus far, compounds that inhibit the methylation or acetylation of histones have advanced in the clinic, but inhibitors of histone phosphorylation have lagged behind. Haspin is a kinase that phosphorylates histone H3 and is a promising anticancer target. Thus far only a handful of haspin inhibitors have been reported. Using a one-flask Doebner/Povarov reaction, we synthesized a library of compounds that potently inhibit haspin with IC50 values as low as 14 nM. Some of these compounds also inhibited the proliferation of cancer cell lines HCT116, HeLa and A375. The ease of synthesis of the new haspin inhibitors, coupled with their anticancer activities make these compounds interesting leads to develop into therapeutics.

The cyclic dinucleotide-cGAS–STING axis plays important roles in host immunity.