Hormetic potential of methylglyoxal, a side-product of glycolysis, in switching tumours from growth to death.

Metabolic reprogramming toward aerobic glycolysis unavoidably favours methylglyoxal (MG) and advanced glycation end products (AGEs) formation in cancer cells. MG was initially considered a highly cytotoxic molecule with potential anti-cancer value. However, we have recently demonstrated that MG enhanced tumour growth and metastasis.

"Breathing" Motion of a Modulable Molecular Cavity.

A class of hemicryptophane cages that adopt imploded conformations in solution and in the solid state has been described and studied by NMR spectroscopy and X-ray crystallography. It is reported that the degree of collapse of the molecular cavity can be controlled by changing the stereochemistry of the chiral elements of the hemicryptophanes, leading to a modulation of their physical and chemical properties. Upon the binding of an oxidovanadium unit, the collapsed molecular cavity can inflate to give an expanded conformation.

Methylglyoxal, a glycolysis side-product, induces Hsp90 glycation and YAP-mediated tumor growth and metastasis.

Metabolic reprogramming toward aerobic glycolysis unavoidably induces methylglyoxal (MG) formation in cancer cells. MG mediates the glycation of proteins to form advanced glycation end products (AGEs). We have recently demonstrated that MG-induced AGEs are a common feature of breast cancer.

Helical, Axial, and Central Chirality Combined in a Single Cage: Synthesis, Absolute Configuration, and Recognition Properties.

The synthesis of eight enantiopure molecular cages (four diastereomeric pairs of enantiomers) comprising a helically chiral cyclotriveratrylene (CTV) unit, three axially chiral binaphthol linkages, and three centrally asymmetric carbon atoms of a trialkanolamine core, is described. These new cages constitute a novel family of hemicryptophanes, which combine three classes of chirality. Their absolute configuration was successfully assigned by a chemical correlation method to overcome the signals overlap in the ECD spectra of the binaphtol and CTV units.

Synthesis of Cryptophanes with Two Different Reaction Sites: Chemical Platforms for Xenon Biosensing.

We report the synthesis of new water-soluble cryptophane host molecules that can be used for the preparation of (129)Xe NMR-based biosensors. We show that the cryptophane-223 skeleton can be modified to introduce a unique secondary alcohol to the propylenedioxy linker. This chemical functionality can then be exploited to introduce a functional group that is different from the six chemical groups attached to the aromatic rings.

Total Synthesis and Reassignment of the Structures of the Antimicrobial Lipodepsipeptides Circulocin γ and δ.

The structures of the naturally occurring antimicrobial lipodepsipeptides circulocin γ and circulocin δ have been reported to comprise a common cyclic depsipeptide core attached to 3-hydroxy,ω-guanidino fatty acid chains differing in length by two methylene units, but analysis of the reported data suggested that the originally reported structures had incorrect side chain lengths. The total synthesis of both side chain epimers of the originally reported structure of circulocin γ bearing a 19-guanidino-3-hydroxynonadecanoyl (GHND) side chain has been accomplished using a modular approach involving synthesis of the cyclic depsipeptide and side chain fragments followed by a late stage coupling reaction. This revealed that the originally reported structure for circulocin γ bearing the GHND side chain is incorrect and that this structure is actually that of circulocin δ.

A new method for peptide synthesis in the N→C direction: amide assembly through silver-promoted reaction of thioamides.

The Ag(I)-promoted coupling of amino acids and peptides with amino ester thioamides generates peptide imides without epimerisation. The peptide imides undergo regioselective hydrolysis under mild conditions to generate native peptides. This method was employed to prepare the pentapeptide thymopentin in the N→C direction, in high yield and purity.

Synthesis of cyclic peptide hemicryptophanes: enantioselective recognition of a chiral zwitterionic guest.

The synthesis of the first members of a new class of cyclic peptide-containing hemicryptophanes is described. Synthesis was achieved through attachment of veratryl groups to the L-tyrosine side chains of a cyclic hexapeptide, c(YG)3, followed by intramolecular cyclodehydration to generate the CTV unit. The diastereomeric P- and M-hemicryptophanes were generated in a 2 : 1 ratio and were separated by chromatography.

A macrolactonization approach to the total synthesis of the antimicrobial cyclic depsipeptide LI-F04a and diastereoisomeric analogues.

The cyclic peptide core of the antifungal and antibiotic cyclic depsipeptide LI-F04a was synthesised by using a modified Yamaguchi macrolactonization approach. Alternative methods of macrolactonization (e.g.

Total synthesis of mycocyclosin.

The first total synthesis of mycocyclosin, a diketopiperazine natural product isolated from M. tuberculosis, is described. While direct oxidative coupling of tyrosine phenolic groups was unsuccessful, construction of the highly strained bicyclic framework was successfully accomplished through an intramolecular Miyaura-Suzuki cross-coupling to generate the biaryl linkage.

Total synthesis and assignment of the side chain stereochemistry of LI-F04a: an antimicrobial cyclic depsipeptide.

The total synthesis of the potent antifungal and antibiotic cyclic depsipeptide LI-F04a and its side chain epimer was accomplished using macrolactonization to assemble the cyclic peptide core, followed by attachment of the 15-guanidino-3-hydroxypentadecanoyl (GHPD) side chain. The side chain was assembled by Yamaguchi-Hirao alkylation of both enantiomers of a chiral epoxide to provide a pair of enantiomeric side chains. The attachment of both these chains to the cyclic peptide allowed the absolute configuration of the side chain hydroxyl group in LI-F04a to be assigned as (R).