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The influence of 2-alkyl-2-carboxyazetidine
s (Aze) on the 3D
structure of model tetrapeptide
s R
2CO-2-R
1Aze-
L-Ala-NHMe ha
s been analyzed by molecular modeling,
1H NMR, and FT-IR
studie
s. Theconformational con
straint
s introduced by the four-membered ring re
sulted in an effective way to
stabilize
![](/image<font color=)
s/gifchar
s/gamma.gif" BORDER=0 >-turn-like conformation
s in the
se
short peptide
s. The conformational preference
s of the
se Aze-containingpeptide
s have been compared to tho
se of the corre
sponding peptide analogue
s containing Pro or
![](/image<font color=)
s/gifchar
s/alpha.gif" BORDER=0>-MeProin the place of 2-alkyl-Aze re
sidue. In the model
studied, both Pro and Aze derivative
s are able to inducerever
se turn
s, but the nature of the turn i
s different a
s a function of the ring
size. While the five-memberedring of Pro tend
s to induce
![](/image<font color=)
s/gifchar
s/beta2.gif" BORDER=0 ALIGN="middle">-turn
s, a
s previou
sly
sugge
sted by different author
s, the four-membered ringof Aze re
sidue
s force
s the peptide to preferentially adopt
![](/image<font color=)
s/gifchar
s/gamma.gif" BORDER=0 >-turn conformation
s. In both ca
se
s, the pre
senceof an alkyl group at the
![](/image<font color=)
s/gifchar
s/alpha.gif" BORDER=0>-po
sition of Pro or the azetidine-2-carboxylate ring enhance
s significantly theturn-inducing ability. The
se re
sult
s might open the opportunity of u
sing 2-alkyl-Aze re
sidue
s a
s ver
satiletool
s in defining the role of
![](/image<font color=)
s/gifchar
s/gamma.gif" BORDER=0 >-turn
structure
s within the bioactive conformation of
selected peptide
s, andrepre
sent an alternative to Pro derivative
s a
s turn inducer
s.