IGR ID=jo701746wn00001>MG SRC="/isubscribe/journals/joceah/73/i05/figures/jo701746wn00001.gif" ALIGN="left" HSPACE=5> |
The
influence of 2-alkyl-2-carboxya
zet
id
ines (A
ze) on the 3D structure of
model tetrapept
ides R
2CO-2-R
1A
ze-
L-Ala-NHMe has been analy
zed by
molecular
model
ing,
1H NMR, and FT-IR stud
ies. Theconfor
mat
ional constra
ints
introduced by the four-
me
mbered r
ing resulted
in an effect
ive way to stab
il
ize
![](/<font color=)
images/g
ifchars/ga
mma.g
if" BORDER=0 >-turn-l
ike confor
mat
ions
in these short pept
ides. The confor
mat
ional preferences of these A
ze-conta
in
ingpept
ides have been co
mpared to those of the correspond
ing pept
ide analogues conta
in
ing Pro or
![](/<font color=)
images/g
ifchars/alpha.g
if" BORDER=0>-MePro
in the place of 2-alkyl-A
ze res
idue. In the
model stud
ied, both Pro and A
ze der
ivat
ives are able to
inducereverse turns, but the nature of the turn
is d
ifferent as a funct
ion of the r
ing s
ize. Wh
ile the f
ive-
me
mberedr
ing of Pro tends to
induce
![](/<font color=)
images/g
ifchars/beta2.g
if" BORDER=0 ALIGN="
middle">-turns, as prev
iously suggested by d
ifferent authors, the four-
me
mbered r
ingof A
ze res
idues forces the pept
ide to preferent
ially adopt
![](/<font color=)
images/g
ifchars/ga
mma.g
if" BORDER=0 >-turn confor
mat
ions. In both cases, the presenceof an alkyl group at the
![](/<font color=)
images/g
ifchars/alpha.g
if" BORDER=0>-pos
it
ion of Pro or the a
zet
id
ine-2-carboxylate r
ing enhances s
ign
if
icantly theturn-
induc
ing ab
il
ity. These results
might open the opportun
ity of us
ing 2-alkyl-A
ze res
idues as versat
iletools
in def
in
ing the role of
![](/<font color=)
images/g
ifchars/ga
mma.g
if" BORDER=0 >-turn structures w
ith
in the b
ioact
ive confor
mat
ion of selected pept
ides, andrepresent an alternat
ive to Pro der
ivat
ives as turn
inducers.