The influence of 2-alkyl-2-carboxyazetidines (Aze) on the 3D structure of model tetrapeptides R
2CO-2-R
1Aze-
L-Ala-NHMe has been analyzed by molecular modeling,
1H NMR, and FT-IR studies. Theconformational constraints introduced by the four-membered ring resulted in an effective way to stabilize
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-turn-like conformations in these short peptides. The conformational preferences of these Aze-containingpeptides have been compared to those of the corresponding peptide analogues containing Pro or
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-MeProin the place of 2-alkyl-Aze residue. In the model studied, both Pro and Aze derivatives are able to inducereverse turns, but the nature of the turn is different as a function of the ring size. While the five-memberedring of Pro tends to induce
![](/images/gifchars/beta2.gif)
-turns, as previously suggested by different authors, the four-membered ringof Aze residues forces the peptide to preferentially adopt
![](/images/gifchars/gamma.gif)
-turn conformations. In both cases, the presenceof an alkyl group at the
![](/images/gifchars/alpha.gif)
-position of Pro or the azetidine-2-carboxylate ring enhances significantly theturn-inducing ability. These results might open the opportunity of using 2-alkyl-Aze residues as versatiletools in defining the role of
![](/images/gifchars/gamma.gif)
-turn structures within the bioactive conformation of selected peptides, andrepresent an alternative to Pro derivatives as turn inducers.