The art of transforming peptides into drug leads is still a powerful and fertile field in medicinal chemistry discovery. Peptidomimetics can respond to peptide limitations by displaying higher metabolic stability, good bioavailability increasing receptor affinity selectivity. Various synthetic approaches strategies have been developed over the years order modulate conformational flexibility nat...

The design and solid-phase synthesis of tetrahydropyridazine-3,6-dione (Tpd) peptidomimetics derived from backbone-aminated peptides is reported. The described protocol features the synthesis of chiral α-hydrazino acids suitable for chemoselective incorporation into growing peptide chains. Acid-catalyzed cyclization to form the Tpd ring during cleavage affords the target peptidomimetics in good...

RGD (Arg-Gly-Asp) peptidomimetics have been designed for covalent anchorage on biomaterials. The tyrosine template was thus equipped with (i) a basic side chain of various flexibility, (ii) an acidic side chain, which incorporated the XPS fluorine tag, and (iii) a spacer-arm terminated by a primary amine for surface grafting. The most active compounds showed IC50 values in the nanomolar range v...

Earlier, we reported the development of a coumarin-based prodrug system that could be used for the preparation of cyclic prodrugs of opioid peptides. These cyclic prodrugs exhibited excellent membrane permeability characteristics. Therefore, it was of interest to determine the effects of this prodrug strategy on the membrane permeabilities of peptidomimetics which also have low membrane permeab...

Macrocyclic peptidomimetics are associated with a broad range of biological activities. However, despite such potentially valuable properties, the macrocyclic peptidomimetic structural class is generally considered as being poorly explored within drug discovery. This has been attributed to the lack of general methods for producing collections of macrocyclic peptidomimetics with high levels of s...

Macrocyclic peptidomimetics are associated with a broad range of biological activities. However, despite such potentially valuable properties, the macrocyclic peptidomimetic structural class is generally considered as being poorly explored within drug discovery. This has been attributed to the lack of general methods for producing collections of macrocyclic peptidomimetics with high levels of s...

The synthesis of eight bifunctional diketopiperazine (DKP) scaffolds is described; these were formally derived from 2,3-diaminopropionic acid and aspartic acid (DKP-1-DKP-7) or glutamic acid (DKP-8) and feature an amine and a carboxylic acid functional group. The scaffolds differ in the configuration at the two stereocenters and the substitution at the diketopiperazinic nitrogen atoms. The bifu...

In the recent past, the design and synthesis of peptide mimics (peptidomimetics) has received much attention. This because they have shown in many cases enhanced pharmacological properties over their natural peptide analogues. In particular, the incorporation of cyclic constructs into peptides is of high interest as they reduce the flexibility of the peptide enhancing often affinity for a certa...