D=jo701746wn00001>MG SRC="/isubscribe/journals/joceah/73/i05/figures/jo701746wn00001.gif" ALIGN="left" HSPACE=5> |
The influence of 2-alkyl-2-carboxyazeti
dines (Aze) on the 3D structure of
mo
del tetrapepti
des R
2CO-2-R
1Aze-
L-Ala-NHMe has been analyze
d by
molecular
mo
deling,
1H NMR, an
d FT-IR stu
dies. Theconfor
mational constraints intro
duce
d by the four-
me
mbere
d ring resulte
d in an effective way to stabilize
mages/gifchars/ga
mma.gif" BORDER=0 >-turn-like confor
mations in these short pepti
des. The confor
mational preferences of these Aze-containingpepti
des have been co
mpare
d to those of the correspon
ding pepti
de analogues containing Pro or
mages/gifchars/alpha.gif" BORDER=0>-MeProin the place of 2-alkyl-Aze resi
due. In the
mo
del stu
die
d, both Pro an
d Aze
derivatives are able to in
ducereverse turns, but the nature of the turn is
different as a function of the ring size. While the five-
me
mbere
dring of Pro ten
ds to in
duce
mages/gifchars/beta2.gif" BORDER=0 ALIGN="
mi
ddle">-turns, as previously suggeste
d by
different authors, the four-
me
mbere
d ringof Aze resi
dues forces the pepti
de to preferentially a
dopt
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 azeti
dine-2-carboxylate ring enhances significantly theturn-in
ducing ability. These results
might open the opportunity of using 2-alkyl-Aze resi
dues as versatiletools in
defining the role of
mages/gifchars/ga
mma.gif" BORDER=0 >-turn structures within the bioactive confor
mation of selecte
d pepti
des, an
drepresent an alternative to Pro
derivatives as turn in
ducers.