LE>jo701746wn00001>SRC="/isubscribe/journals/joceah/73/i05/figures/jo701746wn00001.gif" ALIGN="left" HSPACE=5> |
The inf
luence of 2-a
lky
l-2-carboxyazetidine
s (Aze) on the 3D
structure of mode
l tetrapeptide
s R
2CO-2-R
1Aze-
L-A
la-NHMe ha
s been ana
lyzed by mo
lecu
lar mode
ling,
1H NMR, and FT-IR
studie
s. Theconformationa
l con
straint
s introduced by the four-membered ring re
su
lted in an effective way to
stabi
lize
s/gifchar
s/gamma.gif" BORDER=0 >-turn-
like conformation
s in the
se
short peptide
s. The conformationa
l preference
s of the
se Aze-containingpeptide
s have been compared to tho
se of the corre
sponding peptide ana
logue
s containing Pro or
s/gifchar
s/a
lpha.gif" BORDER=0>-MeProin the p
lace of 2-a
lky
l-Aze re
sidue. In the mode
l studied, both Pro and Aze derivative
s are ab
le to inducerever
se turn
s, but the nature of the turn i
s different a
s a function of the ring
size. Whi
le the five-memberedring of Pro tend
s to induce
s/gifchar
s/beta2.gif" BORDER=0 ALIGN="midd
le">-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 preferentia
lly adopt
s/gifchar
s/gamma.gif" BORDER=0 >-turn conformation
s. In both ca
se
s, the pre
senceof an a
lky
l group at the
s/gifchar
s/a
lpha.gif" BORDER=0>-po
sition of Pro or the azetidine-2-carboxy
late ring enhance
s significant
ly theturn-inducing abi
lity. The
se re
su
lt
s might open the opportunity of u
sing 2-a
lky
l-Aze re
sidue
s a
s ver
sati
letoo
ls in defining the ro
le of
s/gifchar
s/gamma.gif" BORDER=0 >-turn
structure
s within the bioactive conformation of
se
lected peptide
s, andrepre
sent an a
lternative to Pro derivative
s a
s turn inducer
s.