PACE=5> |
The influence of 2-alkyl-2-carboxyazetidines (Aze) on the 3D structure of model tetra
pe
ptides 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
![](/images/gifchars/gamma.gif)
-turn-like conformations in these short
pe
ptides. The conformational
preferences of these Aze-containing
pe
ptides have been com
pared to those of the corres
ponding
pe
ptide analogues containing Pro or
![](/images/gifchars/al<font color=)
pha.gif" BORDER=0>-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
pe
ptide to
preferentially ado
pt
![](/images/gifchars/gamma.gif)
-turn conformations. In both cases, the
presenceof an alkyl grou
p at the
![](/images/gifchars/al<font color=)
pha.gif" BORDER=0>-
position of Pro or the azetidine-2-carboxylate ring enhances significantly theturn-inducing ability. These results might o
pen the o
pportunity 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
pe
ptides, andre
present an alternative to Pro derivatives as turn inducers.