Application of constrained aza-valine analogs for Smac mimicry.

Constrained azapeptides were designed based on the Ala-Val-Pro-Ile sequence from the second mitochondria-derived activator of caspases (Smac) protein and tested for ability to induce apoptosis in cancer cells. Diels-Alder cyclizations and Alder-ene reactions on azopeptides enabled construction of a set of constrained aza-valine dipeptide building blocks, that were introduced into mimics using effective coupling conditions to acylate bulky semicarbazide residues. Evaluation of azapeptides 7-11 in MCF-7 breast cancer cells indicated aza-cyclohexanylglycyine analog 11 induced cell death more efficiently than the parent tetrapeptide likely by a caspase-9 mediated apoptotic pathway.

Investigation of the active turn geometry for the labour delaying activity of indolizidinone and azapeptide modulators of the prostaglandin F2α receptor.

On pursuing molecules that delay labour, so-called tocolytics, the prostaglandin F2α receptor (FP) was targeted, because of its role in the stimulation of uterine contractions leading to birth and preterm birth. Previously, both the indolizidinone PDC-113.824 (5) and the aza-glycinyl-proline analog 6 were shown to delay labour in mice by modulating the FP function, likely by an allosteric mechanism, which features biased signalling.