FIGR ID=jo701746wn00001> figures/jo701746wn00001.gif" ALIGN="left" HSPACE=5> |
The in
fluence o
f 2-alkyl-2-carboxyazetidines (Aze) on the 3D struct
ure o
f model tetrapeptides R
2CO-2-R
1Aze-
L-Ala-NHMe has been analyzed by molecular modeling,
1H NMR, and FT-IR studies. Thecon
formational constraints introduced by the
four-membered ring resulted in an e
ffective way to stabilize
![](/images/gi<font color=)
fchars/gamma.gi
f" BORDER=0 >-turn-like con
formations in these short peptides. The con
formational pre
ferences o
f these Aze-containingpeptides have been compared to those o
f the corresponding peptide analogues containing Pro or
![](/images/gi<font color=)
fchars/alpha.gi
f" BORDER=0>-MeProin the place o
f 2-alkyl-Aze residue. In the model studied, both Pro and Aze derivatives are able to inducereverse turns, but the nat
ure o
f the turn is di
fferent as a
function o
f the ring size. While the
five-memberedring o
f Pro tends to induce
![](/images/gi<font color=)
fchars/beta2.gi
f" BORDER=0 ALIGN="middle">-turns, as previously suggested by di
fferent authors, the
four-membered ringo
f Aze residues
forces the peptide to pre
ferentially adopt
![](/images/gi<font color=)
fchars/gamma.gi
f" BORDER=0 >-turn con
formations. In both cases, the presenceo
f an alkyl group at the
![](/images/gi<font color=)
fchars/alpha.gi
f" BORDER=0>-position o
f Pro or the azetidine-2-carboxylate ring enhances signi
ficantly theturn-inducing ability. These results might open the opportunity o
f using 2-alkyl-Aze residues as versatiletools in de
fining the role o
f ![](/images/gi<font color=)
fchars/gamma.gi
f" BORDER=0 >-turn struct
ures within the bioactive con
formation o
f selected peptides, andrepresent an alternative to Pro derivatives as turn inducers.