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The inf
luence of 2-a
lky
l-2-carboxyazetidines (Aze) on the 3D structure of mode
l tetrapeptides R
2CO-2-R
1Aze-
L-A
la-NHMe has been ana
lyzed by mo
lecu
lar mode
ling,
1H NMR, and FT-IR studies. Theconformationa
l constraints introduced by the four-membered ring resu
lted in an effective way to stabi
lize
-turn-
like conformations in these short peptides. The conformationa
l preferences of these Aze-containingpeptides have been compared to those of the corresponding peptide ana
logues containing Pro or
lpha.gif" BORDER=0>-MeProin the p
lace of 2-a
lky
l-Aze residue. In the mode
l studied, both Pro and Aze derivatives are ab
le to inducereverse turns, but the nature of the turn is different as a function of the ring size. Whi
le the five-memberedring of Pro tends to induce
le">-turns, as previous
ly suggested by different authors, the four-membered ringof Aze residues forces the peptide to preferentia
lly adopt
-turn conformations. In both cases, the presenceof an a
lky
l group at the
lpha.gif" BORDER=0>-position of Pro or the azetidine-2-carboxy
late ring enhances significant
ly theturn-inducing abi
lity. These resu
lts might open the opportunity of using 2-a
lky
l-Aze residues as versati
letoo
ls in defining the ro
le of
-turn structures within the bioactive conformation of se
lected peptides, andrepresent an a
lternative to Pro derivatives as turn inducers.