Designed molecules that fold to mimic protein secondary structures

Downsizing a human inflammatory protein to a small molecule with equal potency and functionality

“…However, the use of proteins in science, industry and medicine is still significantly restricted by their high cost of manufacture, chemical instability, immunogenicity and poor bioavailability. The need to overcome these deficiencies has driven many chemical efforts, but it has been extremely challenging to reproduce the exquisitely potent and specific actions of proteins [1][2][3][4][5][6] . The biological functions of some proteins are localized in very short polypeptide segments stabilized in specific structures (two to four helical turns, isolated b-turns, strands/sheets, and their combinations) by their protein environments 7,8 .…”

Protein/peptide secondary structural mimics: design, characterization, and modulation of protein–protein interactions

“…These acyclic turn mimics have theoretically fullled the purpose of mimic generation on the design level, and they were on the way to being widely applied to more specic PPI target inhibitions. 80 …”

“…63 Kelly's group 64 reported the nucleation of anti-parallel b-sheets in water by harnessing a dibenzofuran unit, which formed a turn structure by folding against the sheet and generating a hydrophobic cluster with the side chains of the neighbouring residues (Fig. 3a).…”

Conformational analysis of hexapseudopeptides mimicking reverse turn structures induced by a modified (S)-proline. A combined spectroscopic and molecular dynamics investigation. Part 4

“…Thus, it is not surprising that a lot of effort is put in the design and synthesis of peptidomimetics (mimicking β-turn structures) as new therapeutic agents. [8][9][10] The importance of replacing natural amino acids in peptides with non-proteinogenic counterparts, in order to obtain drug-like target molecules, has roused a substantial interest in undertaking the synthesis of new peptidomimetic structures that can exhibit therapeutic effects similar to those of natural peptides but with the advantage of metabolic stability (especially proteolitic stability). Common structural modifications that feature these new peptidomimetics usually involve the incorporation of non-natural amino acids in the peptide chain or the use of altered backbones.…”