Macrocyclic small molecules are attractive tools in the development of sensors, new materials, and therapeutics. Within early-stage drug discovery, they are increasingly sought for their potential to interact with broad surfaces of peptidic receptors rather than within their narrow folds and pockets. Cyclization of linear small molecule precursors is a straightforward strategy to constrain conf...

Glycolytic interconversion of phosphoglycerate isomers is catalysed in numerous pathogenic microorganisms by a cofactor-independent mutase (iPGM) structurally distinct from the mammalian cofactor-dependent (dPGM) isozyme. The iPGM active site dynamically assembles through substrate-triggered movement of phosphatase and transferase domains creating a solvent inaccessible cavity. Here we identify...

Nine-membered 1,4,7-triphosphamacrocycles with unsaturated benzo-backbones have been prepared using the [(CO)3Mn](+) unit as a template. Two synthetic methods have been employed for the macrocyclisation both of which involve the attack of a coordinated phosphide at an activated, electrophilic ortho-fluorophenyl substituent on a neighbouring pnictide donor. Addition of base to the precursor comp...

Macrocyclic compounds that can bind cationic species efficiently and selectively with their cyclic cavities have great potential as excellent chemosensors for metal ions. Recently, we have developed a tetraoxime-type tetraazamacrocyclic ligand 1 formed through a facile one-pot cyclization reaction. Aiming to explore and bring out the potential of the tetraoxime macrocycle 1 as a chelating senso...

A macrocyclic trinuclear complex of (1,3,5-trimethylbenzene)ruthenium(II) bridged by 2,3-dioxopyridine was synthesized, and the extraction properties for lithium and sodium picrates were investigated in a dichloromethane/water system at 25 degrees C. The complex was found to have extremely high extractability and selectivity for lithium picrate; the logarithmic values of the extraction constant...

Synthetic amphiphiles have been found to self-assemble into a variety of structures such as micelles, vesicles, cylinders and lamellae in aqueous media over many length scales. We report herein cation-induced aggregation of hexaaza-cyclophanes in water. Pd(2+)- or proton-induced formation of submicro spherical aggregates was observed by several spectroscopic and microscopic methods.

New macrocyclic binuclear nickel(ii) complexes have been synthesized by using the bicompartmental mononuclear complex [NiL] [3,30-((1E,7E)-3,6-dioxa-2,7-diazaocta-1,7-diene-1,8-diyl)bis(3-formyl-5-methyl-2-diolato)nickel(II)] with various diamines like 1,2-bis(aminooxy)ethane (L(1)), 1,2-diamino ethane (L(2)), 1,3-diamino propane (L(3)), 1,4-diamino butane (L(4)), 1,2-diamino benzene (L(5)), an...

Macrocyclic peptides can interfere with challenging biomolecular targets including protein-protein interactions. Whereas there are various approaches that facilitate the identification of peptide-derived ligands, their evolution into higher affinity binders remains a major hurdle. We report a virtual screen based on molecular docking that allows the affinity maturation of macrocyclic peptides t...

This research explores the first design and synthesis of macrocyclic peptide aldehydes as potent inhibitors of the 20S proteasome. Two novel macrocyclic peptide aldehydes based on the ring-size of the macrocyclic natural product TMC-95 were prepared and evaluated as inhibitors of the 20S proteasome. Both compounds inhibited in the low nanomolar range and proved to be selective for the proteasom...