Prolinoamino Acids as Tools to Build Bifunctionalized, Stable β‐Turns in Water

Synthesis and conformational studies of peptido-squaramide foldable modules: a new class of turn-mimetic compounds

“…5,9 In the latter, when the conformational control is needed, one useful strategy is the incorporation of proline residues to stabilise the folded conformation due to its β-turn propensity. 10 Alternatively, other foldable modules of a different nature can be used as proline substitutes. In this context, for example, β, γ, and δ-amino acids have proved to encourage turn formation 11 and a combination of several non-natural residues of an aliphatic or aromatic nature are well suited to serve as turn mimetics or β-hairpin initiators.…”

3-Substituted Prolines: From Synthesis to Structural Applications, from Peptides to Foldamers

“…The pyrrolidine cycle restricts the side chain conformational space since only two of the three possible χ1 canonical rotamers of unconstrained amino acids are accessible to prolinoamino acids, the trans and a single gauche rotamer (g − or g + for trans or cis -prolinoamino acids, respectively). Although the geometrical constraint due to the cyclization induces a 30° deviation of χ1 from ideal staggered values, the conformers of prolinoamino acids fit well with the corresponding structures of unconstrained amino acids [ 48 , 50 ].…”

“…The β-turn motif, a recognition element often involved in receptor-ligand interactions [ 65 ], is a major subject of investigation in the development of synthetic mimics of peptide secondary structure [ 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 ]. The use of cis -3-substituted prolinoamino acids in combination with N -methyl- or cyclopropyl amino acids has been reported to stabilize type II’ β-turns in water that retain the side-chain functionalities in both i+1 and i+2 positions of the turn [ 50 , 68 ]. These short peptides incorporate three motifs, a heterochiral sequence, a proline scaffold and a N -methyl group or a cyclopropylamino acid, that are known to exhibit strong β-turn propensity ( Figure 5 ) [ 1 , 73 , 74 , 75 ].…”

Homooligomers of substituted prolines and β-prolines: syntheses and secondary structure investigation

“…13,14,[18][19][20][21][22] These monomers allow combining the conformational constraints and lack of hydrogen-bond donor of the proline residue in a peptide while keeping the opportunity to decorate them with proteinogenic side chains. We have shown that these residues can be used to build functionalized b-turns that are stable in water, 23 or to introduce a specific functional group in PPII folded peptides that inhibit peptide-protein 24 or proteinprotein interaction. 25 Recently the carbocyclization synthetic strategy has been applied to the preparation of b-proline analogues substituted at position 4 (Fig.…”