MG SRC="/isubscribe/journals/joceah/73/i05/figures/jo701746wn00001.gif" ALIGN="left" HSPACE=5> |
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. Theconfor
mational constraints introduced by the four-
me
mbered ring resulted in an effective way to stabilize
mages/
gifchars/ga
mma.
gif" BORDER=0 >-turn-like confor
mations in these short peptides. The confor
mational preferences of these Aze-containingpeptides have been co
mpared to those of the corresponding peptide analogues containing Pro or
mages/
gifchars/alpha.
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-
me
mberedring of Pro tends to induce
mages/
gifchars/beta2.
gif" BORDER=0 ALIGN="
middle">-turns, as previously suggested by different authors, the four-
me
mbered ringof Aze residues forces the peptide to preferentially adopt
mages/
gifchars/ga
mma.
gif" BORDER=0 >-turn confor
mations. In both cases, the presenceof an alkyl group at the
mages/
gifchars/alpha.
gif" BORDER=0>-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
mages/
gifchars/ga
mma.
gif" BORDER=0 >-turn structures within the bioactive confor
mation of selected peptides, andrepresent an alternative to Pro derivatives as turn inducers.