Design of peptides with α,β-dehydro-residues: Synthesis, crystal structure and molecular conformation of a peptide N-tertiary-butyloxycarbonyl-L-Leu-ΔPhe-L-Ile-OCH3

Article abstract of DOI:10.1016/S0022-2860(03)00464-2

In order to develop new design rules with dehydro-residues a peptide tertiary-butyloxycarbonyl-L-Leu-ΔPhe-L-Ile-OCH₃ was synthesized. The synthesis was carried out in solution using azlactone procedure. The three-dimensional structure of the peptide was determined by X-ray diffraction method and refined to an R-factor of 0.065. The peptide adopts an unfolded S-shaped conformation with φ₁ = -78.8(6)°, ψ₁ = -28.5(7)°, ψ₂ = 51.8(7)°, ψ ₂ = 44.6(7)°, ψ₃ = -93.7(7)°, ψ ₃^T = 21.5(7)°. This is the first example of a characteristic unfolded conformation of a peptide having ΔPhe at (i + 2) position with a single branched β-carbon residue. The side chain conformation of Ile with χ^1,1 = 60.5(8)° χ^1,2 = -66.7(7)° is not in a favourable form thus causing strong steric constraints. The crystal packing is stabilized by two intermolecular hydrogen bonds N₁ - H₁ ? O₂′ = 2.936(6) A? and N₃ - H₃ ? O₁′ = 3.096(6) A? and a number of van der Waals interactions involving side chains of Leu, ΔPhe and Ile as one block and the Boc groups from neighbouring peptide molecules as the second block.

Full text of DOI:10.1016/S0022-2860(03)00464-2

Journal of Molecular Structure 658 (2003) 135–141
www.elsevier.com/locate/molstruc
Design of peptides with a,b-dehydro-residues: synthesis,
crystal structure and molecular conformation of a peptide
N-tertiary-butyloxycarbonyl-L-Leu-DPhe-L-Ile-OCH3
*
V.K. Goel, M. Guha, A.P. Baxla, S. Dey, T.P. Singh
Department of Biophysics, All India Institute of Medical Sciences, New Delhi 110029, India
Received 27 June 2003; revised 15 July 2003; accepted 17 July 2003
Abstract
In order to develop new design rules with dehydro-residues a peptide tertiary-butyloxycarbonyl-L-Leu-DPhe-L-Ile-OCH
3
was synthesized. The synthesis was carried out in solution using azlactone procedure. The three-dimensional structure of
the peptide was determined by X-ray diffraction method and refined to an R-factor of 0.065. The peptide adopts an
unfolded S-shaped conformation with f ¼ 278:8ð6Þ8; c ¼ 228:5ð7Þ8; f ¼ 51:8ð7Þ8; c ¼ 44:6ð7Þ8; f ¼ 293:7ð7Þ8;
1
1
2
2
3
T
3
c ¼ 21:5ð7Þ8: This is the first example of a characteristic unfolded conformation of a peptide having DPhe at ði þ 2Þ
1;1
1;2
position with a single branched b-carbon residue. The side chain conformation of Ile with x ¼ 60:5ð8Þ8 x ¼ 266:7ð7Þ8
is not in a favourable form thus causing strong steric constraints. The crystal packing is stabilized by two intermolecular
ꢀ
0
ꢀ
0
hydrogen bonds N –H · · ·O ¼ 2:936ð6Þ A and N –H · · ·O ¼ 3:096ð6Þ A and a number of van der Waals interactions
1
1
2
3
3
1
involving side chains of Leu, DPhe and Ile as one block and the Boc groups from neighbouring peptide molecules as the
second block.
q 2003 Elsevier B.V. All rights reserved.
Keywords: Peptide design; X-ray diffraction; DPhe residue; Conformation; Crystal structure
1
. Introduction
suggest ways to develop a set of design rules.
The a,b-dehydro-residues have been found to
induce characteristic constraints which can be
defined and hence can be exploited as predictable
design tools to generate specific conformations. It
has already been shown that a DPhe residue adopts
only three conformations, defined by f=c torsion
angle values 260/140, 80/0 and 260/2308,
respectively [1]. Furthermore, these torsion angle
values of DPhe residue are linked to its specific
location in the peptide sequence. For example, a
DPhe residue at ði þ 2Þ position, induces a type II
Short linear peptides are generally very flexible
and hence can adopt a large number of confor-
mations thus making the prediction of their
structures very difficult. In order to design the
required structures, it is necessary to develop tools
that restrict the number of conformations and
*
Corresponding author. Tel.: þ91-11-26593201; fax: þ91-11-
6588663.
E-mail address: tps@aiims.aiims.ac.in (T.P. Singh).
2
0022-2860/03/$ - see front matter q 2003 Elsevier B.V. All rights reserved.
doi:10.1016/S0022-2860(03)00464-2

136
V.K. Goel et al. / Journal of Molecular Structure 658 (2003) 135–141
b-turn conformation with f=c values of 80/08 [1]
while at ði þ 1Þ position it adopts a conformation
with f; c torsion angles 260, 1408 also resulting
in the formation of a b-turn II conformation [1]
indicating its preference of being accommodated in
a type II b-turn conformation at both ði þ 1Þ and
ði þ 2Þ positions. The sequences longer than tetra-
peptides containing more than one DPhe residues,
irrespective of their locations in the peptides, adopt
a repetitive 3 -helical conformation with torsion
2. Experimental
The peptide Boc-Leu-DPhe-Ile-OCH
thesized using the following steps.
was syn-
3
2.1. Synthesis of Boc-Leu-(b-OH)-Phe-OH (1)
To a precooled solution (10 8C) of Boc-L-Leu-OH
(
(
3 g, 13.8 mmol) in dry tetrahydrofuran (THF)
10 ml), N-methylmorpholine (NMM) (1.51 ml,
1
0
1
3.8 mmol) and isobutylchloroformate (IBCF)
1.79 ml, 13.8 mmol) were added. After 15 min of
stirring a solution of DL-(b-OH)-Phe-OH (3.0 g,
6.5 mmol) in 1N NaOH (16.5 ml) was added to it
angles of 260, 2308 [1]. In order to develop
design rules with DPhe residue, it is necessary to
work out all the combinations and permutations of
various saturated residues with respect to the DPhe
residue. Since the branched b-carbon residues Val
and Ile show unique conformational preferences
with respect to the peptide backbone [2], their
combinations with a DPhe residue may also induce
different conformations in the peptide backbones.
Therefore, the systematic investigations of peptides
containing both branched b-carbon and DPhe
residues in various combinations are required to
be carried out. So far, the crystal structure of a
peptide Boc-Phe-DPhe-Val-OCH3 [3,4] with a
single branched b-carbon residue Val at ði þ 3Þ
position reported the formation of a highly
distorted type II b-turn conformation with a
characteristic intramolecular 4 ! 1 hydrogen bond.
The introduction of two branched b-carbon residues
Val/Ile at both ði þ 1Þ and ði þ 3Þ position in Boc-
Val-DPhe-Val-OCH [5], Boc-Val-DPhe-Ile-OCH
(
1
and the mixture was stirred at 0 8C. The resulting oily
compound was obtained with a yield ¼ 4.6 g (68%),
R ¼ 0:45 (CHCl :MeOH < 9:1).
f
3
2.2. Boc-L-Leu-DPhe azlactone (2)
Compound (1) (4.6 g, 12.1 mmol) was reacted with
anhydrous sodium acetate (1.0 g, 12.1 mmol) and
freshly distilled acetic anhydride (10 ml) for 96 h at
room temperature. The yield was: 3.5 g (74%), R ¼
f
0
:97 (CHCl :MeOH < 9:1).
3
2.3. Boc-L-Leu-DPhe-L-Ile-OCH (I)
3
To a solution of compound (2) (1.0 g, 3.0 mmol) in
dichloromethane (DCM), Ile-OCH ·HCl (0.91 g,
3
3
.6 mmol) neutralized by triethylamine (TEA)
0.5 ml, 3.6 mmol) was added and the solution was
3
3
(
stirred for 72 h at room temperature. The yield of
[
6] and Boc-Ile-DPhe-Ile-OCH3 [7] completely
disrupted the formation of a commonly observed
b-turn II conformation with a DPhe at ði þ 2Þ
position. As expected, these results indicated that
the combination of branched b-carbon residue/
residues and a DPhe residue induced different
steric effects on the peptide backbone than those
observed with the combination of DPhe and non-
branched b-carbon residues [1]. In order to
complete the systematic studies on the peptide
design with branched b-carbon residues, a peptide
peptide (I) was: 0.98 g (72%), R ¼ 0:58 (CHCl :
f
3
MeOH < 9:1).
1
.4. H-NMR of Boc-Leu-DPhe-Ile-OCH
2
3
In order to confirm the correctness of the final
1
synthesis of the peptide, H-NMR spectra were
recorded in CDCl with 400 MHz Bruker DRX 400
3
instrument and the following results were obtained: d
g2
d
d
.88–0.95 (m, 12H, C , C Ile, C Leu); d 1.04–1.06
0
(m, 2H, C Ile); d 1.2 (m, 4H, C , C , Leu); d 1.4 (s,
g1
b
g
Boc-Leu-DPhe-Ile-OCH with Ile at ði þ 3Þ position
3
g1
9H, t-Bu, Boc); d 1.77 (m, 3H, C , C Ile); d 3.74 (s,
b
was synthesized and its three-dimensional structure
was determined by X-ray diffraction methods. The
structure showed that the combination of DPhe-Ile
induced unfolded S-shaped conformation.
a
3H, OCH ); d 4.2 (q, C , Leu) d 4.46 (m, 1H, C Ile);
a
3
d 5.14 (bd, 1H, NH, Leu); d 7.26–7.28 (m, 6H, DPhe,
b
C DPhe); d 7.52 (s, 1H, NH DPhe), d 8.71 (s, 1H, NH

V.K. Goel et al. / Journal of Molecular Structure 658 (2003) 135–141
137
1
Ile). The observed H-NMR spectra clearly indicated
2955 observed reflections ½I $ 2sðIÞꢀ was 0.065.
The details of intensity data collection and refine-
ment are also given in Table 1. The atomic
scattering factors used in these calculations were
those of Cromer and Mann [10] for non-hydrogen
atoms and Stewart et al. [11] for hydrogen atoms.
The final positional and equivalent isotropic thermal
parameters of non-hydrogen atoms are given in
Table 2.
the presence of peptide Boc-Leu-DPhe-Ile-OCH in
3
the solution.
2
.5. Structure determination
The peptide was crystallised from its solution in
methanol—water mixture at room temperature
298 K) by slow evaporation method. The crystal
(
data are given in Table 1. The unit cell parameters
were refined by a least-squares fit of 25 high angle
ð25 # u # 408Þ reflections. These reflections were
centred individually on the diffractometer. Lorentz
and polarisation corrections were applied. However,
the absorption corrections were not applied due to
small size of the crystal. The structure was
determined by direct methods using the program
SHELXS 97 [8]. The coordinates of non-hydrogen
atoms were refined anisotropically using program
SHELXL 97 [9]. The coordinates of hydrogen atoms
were obtained from difference Fourier map and were
included in the final cycles of refinement using
isotropic temperature factors of non-hydrogen atoms
to which they were attached. The final R-factor for
Table 2
4
Atomic coordinates ( £ 10 ) and equivalent isotropic thermal
3
parameters ( £ 10 ) of non-hydrogen atoms in Boc-Leu-DPhe-Ile-
OCH
3
(estimated standard deviations are given in parentheses)
2
Ueq (A )
a
˚
Atoms
x
y
z
C
01
4917(9)
2265(9)
3775(10)
3660(8)
3492(4)
4553(7)
5674(5)
4161(5)
5268(6)
4736(7)
4648(10)
3792(11)
6124(12)
5713(6)
6923(4)
4759(5)
5019(6)
4846(7)
4470(7)
3881(9)
3527(10)
3828(10)
4435(10)
4757(8)
5461(6)
6388(4)
4707(5)
4959(7)
5030(7)
3652(8)
6346(8)
3582(11)
3968(7)
3798(6)
3440(5)
2669(10)
P P
11,972(4)
11,970(5)
11,692(5)
11,584(4)
10,631(2)
10,045(4)
10,223(3)
9222(3)
8546(3)
7791(4)
8019(5)
7329(7)
8096(8)
8144(3)
7829(3)
8115(3)
7627(3)
7924(4)
8807(4)
8876(5)
9690(6)
10,443(5)
10,409(6)
9584(4)
6673(3)
6337(3)
6211(3)
5271(4)
5007(4)
5210(5)
5414(5)
4774(6)
4688(4)
3915(3)
5111(3)
4564(6)
10,813(5)
10,718(5)
9739(4)
74(2)
81(3)
72(2)
50(2)
46(1)
40(1)
57(1)
36(1)
35(1)
45(1)
68(2)
103(3)
111(4)
34(1)
45(1)
32(1)
34(1)
45(1)
46(2)
63(2)
85(3)
77(3)
75(2)
55(2)
35(1)
42(1)
40(1)
42(1)
50(2)
59(2)
61(2)
94(3)
49(2)
79(2)
60(1)
82(3)
C02
C
C
03
0
10,468(3)
10,637(2)
10,503(3)
10,248(2)
10,693(2)
10,742(3)
11,184(3)
11,891(3)
12,255(4)
12,193(4)
10,097(2)
10,038(2)
9618(2)
O
0
0
C
0
0
O
0
N1
a
C
C
C
C
C
C
1
b
1
g
1
d1
1
d2
1
0
0
Table 1
The details of intensity data collection and refinement for Boc-L-
Leu-DPhe-L-Ile-OCH
3
1
O
1
Molecular formula
Molecular weight
Crystal system
Space group
C
27
H
41
N
3
O
6
N
2
a
503.63
C
C
C
C
C
C
C
C
C
2
b
2
g
2
d1
2
1
2
z
2
12
2
d2
2
0
9043(2)
Orthorhombic
8445(3)
P2 2 2
1 1
8196(3)
1
˚
a (A)
˚
b (A)
9.376(1)
15.092(2)
20.579(3)
2911.9(7)
4
7582(3)
1
7318(4)
˚
c (A)
7644(4)
3
˚
V (A )
8256(4)
Z (molecules/unit cell)
2
D (g cm
c
8521(3)
3
)
1.149
2
9129(2)
0
Fð000Þ
1091
O
2
8786(2)
Total number of independent reflections
2955
N
3
a
9568(2)
Number of observed reflections ðI $ 2sðIÞÞ 2082
C
C
C
C
C
C
3
b
3
g1
3
g2
3
d
3
0
0
9671(3)
˚
Radiation (l, Cu Ka/A)
mr
Instrument used
1.5418
10,381(3)
10,742(4)
10,706(4)
11,404(4)
9265(3)
0.659
Enraf–Nonius CAD4
v 2 2u
Mode of data collection
3
Crystal dimension (mm )
0.4 £ 0.2 £ 0.2
0.065
3
R
O
3
9371(3)
Rw
0.2094
O
4
8757(2)
S (Goodness of fit)
Temperature (K)
1.284
C
4
8294(4)
293
a
Ueq ¼ ð1=3Þ
U a a ða ·a Þ:
i
j
ij
i
j
i
j

138
V.K. Goel et al. / Journal of Molecular Structure 658 (2003) 135–141
3
Fig. 1. Stereoview of the peptide Boc-Leu-DPhe-Ile-OCH . The residues are labelled.
3
. Results and discussion
3.1. Molecular dimensions
a
The C yC double bond length in DPhe is
˚
1.320(8) A. The values of neighbouring bond lengths
b
The stereoview of the peptide Boc-Leu-DPhe-Ile-
OCH is shown in Fig. 1. The peptide molecule is
characterized by an unfolded S-shaped conformation
3
a
b
g
˚
˚
N –C ¼ 1.415(7) A and C –C ¼ 1.470(8) A indi-
2
2
2
2
with f=c torsion angles f ¼ 278:8ð8Þ8; c ¼
cate that they are significantly shorter than the
respective single bond length distances in saturated
residues [12]. Similarly, the important bond angles in
1
1
2
2
28:5ð7Þ8; f ¼ 51:8ð7Þ8; c ¼ 44:6ð7Þ8; f ¼
2
2
3
T
3
93:7ð7Þ8; c ¼ 21:5ð7Þ8:
Fig. 2. A schematic drawing of the peptide Boc-Leu-DPhe-Ile-OCH
to 3.
3
indicating the relevant torsion angles. The residues are numbered from
0

V.K. Goel et al. / Journal of Molecular Structure 658 (2003) 135–141
139
a
0
a
Table 3
DPhe residue N –C –C ¼ 116.5(4)8 and N –C –
2
2
2
2
2
b
2
a
2
b
2
g
2
Selected torsion angles (8) involving non-hydrogen atoms in Boc-
(estimated standard deviations are given in
C ¼ 125.6(5)8 and C –C –C ¼ 131.5(6)8 are also
Leu-DPhe-Ile-OCH
parentheses)
3
significantly deviated from the normal value of 1208.
As observed in the DPhe residue of other peptide
structures, these deviations in geometry occur com-
monly and are needed to release the increased steric
effects in the DPhe residue due to enhanced planarity
0
u0
C
0
–O
0
0
–C
0
–N
–C
1
a
1
0
2 179.5(5)
2165.0(4)
278.9(6)
271.6(7)
166.2(6)
271.8(8)
228.5(7)
2169.8(4)
51.8(7)
v0
O
0
–C
–N
–C
0
–N
1
a
0
f1
C
0
1
–C
1
–C
1
g
a
1
b
x1
N
1
a
1
a
1
–C
1
–C
–C
–C
1
d1
1
d2
1
a
b
2;1
b
g
and shortening of the distance between C and C in
2 2
x
x
c
C
C
–C
–C
1
b
1
–C
–C
1
g
1
1
2
;2
DPhe residue [1].
.2. Conformation of the peptide
The peptide Boc-L-Leu-DPhe-L-Ile-OCH (Fig. 2)
2
a
1
0
0
1
N
1
–C
–C
–N
1
–N
2
a
1
0
a
2
0
v
f
1
C
–C
1
2
a
2
–C
3
C
1
–N
–C
2
–C
–C
2
2
1
a
2
b
g
2
d2
2
d1
2
x
x
x
N
2
a
2
a
2
–C
2
–C
–C
–C
5.3(11)
2
2
;2
b
g
3
C
C
–C
–C
2
b
2
–C
–C
2
g
2
26.8(11)
2157.7(7)
44.6(7)
2
2
2
;1
adopts a characteristic S-shaped conformation with
torsion angles f ¼ 278:8ð8Þ8; c ¼ 228:5ð7Þ8;
a
2
0
0
c
2
N
2
–C
–C
–N
2
–N
3
1
1
a
2
0
a
3
0
T
v
f
2
C
–C
2
3
a
3
–C
176.1(5)
293.7(7)
60.5(8)
f ¼ 51:8ð7Þ8; c ¼ 44:6ð7Þ8; f ¼ 293:7ð7Þ8; g ¼
2
2
3
3
C
2
–N
–C
–C
3
–C
–C
3
3
2
1:5ð7Þ8 (Table 3). Similar conformations have been
1;1
a
3
a
3
b
g1
3
g2
3
x
x
x
N
N
3
–C
–C
–C
3
b
3
–C
3
1
;2
observed in peptides containing two branched b-
carbon residues one on each side of the DPhe
residues, Boc-Val-DPhe-Val-OCH3 [5], Boc-Val-
DPhe-Ile-OCH3 [6] and Boc-Ile-DPhe-Ile-OCH3
3
a
3
–C
266.7(7)
167.4(6)
21.5(7)
3
2
3
T
;1
b
g1
3
d1
C
–C
3
a
3
–C
3
0
c3
N
3
–C
–C
3
–O
4
[7]. As seen from Table 4, it is noteworthy that
Table 4
The backbone torsion angles (8) of peptides (1) Boc-Phe-DPhe-Val-OCH
3
, (2) Boc-Val-DPhe-Val-OCH
3
3
, (3) Boc-Val-DPhe-Ile-OCH , (4)
Boc-Ile-DPhe-Ile-OCH , (5) Boc-Leu-DPhe-Ile-OCH
3
3
(present study)
T
Peptide f1
c1
f2
c2
f3
c3
Reference
(1)
(2)
(3)
(4)
(5)
243.3(2)
2128(2)
2127(1)
2124.18(3)
278.8(8)
134.3(2)
237(2)
243(1)
46.5(2)
65(1)
38.0(4)
35(1)
251.7(2)
284(1)
282(1)
137.0(1)
169(1)
[3,4]
[5]
67(1)
37(1)
145(2)
[6]
162.39(3)
228.5(7)
51.0(3)
51.8(7)
36.8(3)
44.6(7)
2117.9(3)
293.7(7)
167.3(2)
21.5(7)
[7]
Present study
Table 5
The side chain torsion angles (8) of Val/Ile in DPhe-Val/Ile moiety (1) Boc-Phe-DPhe-Val-OCH
DPhe-Ile-OCH , (4) Boc-Ile-DPhe-Ile-OCH , (5) Boc-Leu-DPhe-Ile-OCH (present study), (6) Boc-Val-DPhe-DPhe-Val-OCH
DPhe-DPhe-Ile-OCH , (8) Cbz-DVal-Val-DPhe-Ile-OCH
3
, (2) Boc-Val-DPhe-Val-OCH
3
, (3) Boc-Val-
3
3
3
3
, (7) Boc-Val-
3
3
1
3
;1
1;2
1;1
1;2
Peptide
Val/Ile
x
x3
x4
x4
Reference
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
Val
Val
263.7(5)
174(1)
122(3)
271.1(5)
60.5(8)
–
169.5(4)
257(2)
2137(3)
54.9(5)
266.7(7)
–
–
–
[3,4]
–
–
[5]
a
Ile
–
–
[6]
Ile
Ile
Val
Ile
Ile
–
–
[7]
–
–
Present study
[15]
178.2(4)
267.9(8)
69.2(9)
258.9(6)
57.6(8)
258.6(9)
–
–
[14]
–
–
[16]
a
Side chain structure of Ile is disordered.

140
V.K. Goel et al. / Journal of Molecular Structure 658 (2003) 135–141
the presence of a branched b-carbon residue Val at
ði þ 3Þ position does not prevent the formation of a
commonly observed b-turn II conformation with
DPhe at ði þ 2Þ position, but the conformation of the
peptide is highly distorted. In the present case with
Ile at ði þ 3Þ position, the b-turn conformation was
completely lost. Therefore, the constraints caused by
placing Ile next to DPhe are more pronounced than
those introduced by the presence of DPhe-Val
moiety at the same position. In view of this, the
present structure provides a new information for
extending design rules further with dehydro-resi-
dues. As seen from Table 3, the side chain torsion
1
2;2
2
2;2
and x2 are 5.3(11),
angles of DPhe x ; x
2
26.8(11) and 2157.7(7)8, respectively, which rep-
resent a conformation that has not been observed for
the saturated Phe residue [13] but are similar to
those found in DPhe of the other peptide structures
[1]. The conformation of side chains of Leu and Ile
2
1
;1
residues are x ¼ 271:6ð7Þ8;
x
¼ 166:2ð6Þ8;
1
2
1
;2
1;1
3
1;2
x
¼ 271:8ð8Þ8
and
x
¼ 60:5ð8Þ8
x
3
¼
2
;1
266:5ð8Þ8; x ¼ 167:4ð6Þ8; respectively.
3
3
Fig. 3. A view of the crystal packing of peptide Boc-Leu-DPhe-Ile-OCH . The hydrogen bonds are indicated by dotted lines.

V.K. Goel et al. / Journal of Molecular Structure 658 (2003) 135–141
141
The side chain torsion angles for Leu residue
indicate that it adopts a more commonly observed con-
formation for Leu residue in peptides [13]. However,
4. a DPhe residue at ði þ 2Þ position with branched b-
carbon residues Val/Ile at both ði þ 1Þ and ði þ 3Þ
positions produces an unfolded S-shaped confor-
mation [5,6].
1
;1
1;2
the side chain torsion angle values of x and x
Fig. 2) in Ile do not adopt a staggered conformation as
(
observed for Val when placed next to the DPhe
residues [14]. Hence, Ile is likely to have caused
considerable steric effects on the neighbouring DPhe
residue thus preventing the formation of a commonly
observed type II b-turn conformation. As seen from
Table 5, it is noteworthy that the Val side chain, when
placed next to the DPhe residue always adopts a stag-
The reproducible nature of these observations
suggests that the DPhe residue based design of
peptides can provide a variety of definitely predictable
conformations and hence can be usefully applied for
ligand design.
1
;1
1;2
gered conformation with x ; x values in the neigh-
bourhood of ^60, ^180 while the corresponding side
chain torsion angles in Ile are found in the neighbour-
hood of ^60, ^60 thus producing considerably higher
steric effects than caused by the side chain of Val.
Acknowledgements
The authors thank Council of Scientific and
Industrial Research (CSIR), New Delhi for financial
support.
3
.3. Molecular packing and hydrogen bonding
References
The packing of molecules in the unit cell is shown
in Fig. 3. The structure is stabilized by two
intermolecular hydrogen bonds formed involving
NH groups of Leu and Ile residues with CO groups
of symmetry related DPhe and Leu residues, respect-
[
1] T.P. Singh, P. Kaur, Prog. Biophys. Mol. Biol. 66 (1996) 141.
[2] J.S. Richardson, Adv. Protein Chem. 34 (1981) 167.
[
[
3] T.P. Singh, M. Haridas, V.S. Chauhan, A. Kumar, Biopoly-
mers 26 (1987) 816.
4] T.P. Singh, M. Haridas, V.S. Chauhan, A. Kumar, D. Viterbo,
Biopolymers 27 (1988) 1333.
0
˚
ively, [N –H · · ·O ¼ 2.936(6) A and N3 –
1
1
2
0
˚
H · · ·O ¼ 3.094(6) A]. The packing is also stabilized
3
1
[5] S.N. Mitra, S. Dey, S. Bhatia, T.P. Singh, Int. J. Biol.
Macromol. 19 (1996) 103.
by van der Waals interactions involving the side
chains of Leu, DPhe and Ile residues and the terminal
[
[
[
6] S. Dey, S.N. Mitra, T.P. Singh, Int. J. Peptide Protein Res. 48
1996) 123.
7] J. Makker, S. Dey, P. Kumar, T.P. Singh, Z. Kristallogr. NCS
18 (2003) in Press.
(
Boc and OCH groups.
3
2
8] G.M. Shedrick, SHELXS 97, A Program for the Determination
of Crystal Structures, Anorganisch-Chemisches Institut der
Universit a¨ t, G o¨ ttingen, Germany, 1997.
4
. Conclusions
[
9] G.M. Shedrick, SHELXL 97, A Program for the Refinement of
Crystal Structures, Anorganisch-Chemisches Institut der
Universit a¨ t, G o¨ ttingen, Germany, 1997.
The structures of peptides determined so far with
DPhe at ði þ 2Þ position indicate that
[
10] D.T. Cromer, J.B. Mann, Acta Crystallogr. A24 (1968) 321.
[11] R.F. Stewart, E.R. Davidson, W.T. Simpson, J. Chem. Phys.
2 (1965) 3175.
1
. a DPhe residue at ði þ 2Þ position with non-
branched b-carbon residues at ði þ 1Þ and ði þ 3Þ
positions induces a type II b-turn conformation [1].
. a DPhe residue at ði þ 2Þ position with Val at
ði þ 3Þ and non-branched b-carbon residue at
ði þ 1Þ position produces a substantially distorted
b-turn II conformation [3,4].
4
[
12] R.E. Dickerson, I. Geis, The Structure and Action of Proteins,
Harper and Row, New York, USA, 1969, p. 13.
2
[
13] E. Benedetti, in: M. Goodman, J. Meienhofer (Eds.), Peptides,
Proceedings of the Fifth American Peptide Symposium,
University of California, San Diego, Wiley, New York,
1
977, p. 257.
14] S. Bhatia, P. Kumar, P. Kaur, T.P. Singh, J. Peptide Res. 54
1999) 249.
[
3
. a DPhe residue at ði þ 2Þ position with Ile at ði þ 3Þ
position and a non-branched b-carbon residue at
ði þ 1Þ position generates an unfolded S-shaped
conformation (present study).
(
[
[
15] S. Dey, S.N. Mitra, T.P. Singh, Biopolymers 39 (1996) 49.
16] J. Makker, S. Dey, S. Mukherjee, P. Kumar, T.P. Singh, J. Mol.
Struct. 654 (2003) 119.