Secondary structure binding motifs of the jet cooled tetrapeptide model Ac-Leu-Val-Tyr(Me)-NHMe

Article abstract of DOI:10.1039/b706519a

In this paper the structure of the isolated tetrapeptide model Ac-Leu-Val-Tyr(Me)-NHMe (Leu = leucine, Val = valine, Tyr = tyrosine) is investigated by mass- and isomer-selective IR/UV double resonance spectroscopy. Two isomers of this peptide are observe

Full text of DOI:10.1039/b706519a

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PCCP themed issue on
Spectroscopic probes of
molecular recognition
Guest edited by Martin Suhm
(Universität Göttingen)
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Michel Mons from Phys. Chem. Chem.
Phys., 2007, 9, 4491
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Chem. Chem. Phys., 2007, 9, 4452
Published in issue 32, 2007 of PCCP
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PAPER
www.rsc.org/pccp | Physical Chemistry Chemical Physics
Secondary structure binding motifs of the jet cooled tetrapeptide model
Ac–Leu–Val–Tyr(Me)–NHMe
a
b
c
a
¨
H. Fricke, G. Schafer, T. Schrader and M. Gerhards*
Received 30th April 2007, Accepted 11th July 2007
First published as an Advance Article on the web 25th July 2007
DOI: 10.1039/b706519a
In this paper the structure of the isolated tetrapeptide model Ac–Leu–Val–Tyr(Me)–NHMe
(Leu = leucine, Val = valine, Tyr = tyrosine) is investigated by mass- and isomer-selective IR/
UV double resonance spectroscopy. Two isomers of this peptide are observed and in combination
with force field, ab initio, and DFT calculations these structures are assigned to folded
arrangements presenting two different secondary structure binding motifs: (a) a combined g-turn/
b-turn structure and (b) a triple g-turn structure, which is described for the first time for an
isolated model system in the gas phase.
I. Introduction
uous assignment to a certain structure. The tetrapeptide model
offers several structural arrangements including b-sheet related
structures, b-turns, g-turns as well as combined structural
arrangements like b-turn/g-turn conformations.
Flexible biomolecules like peptides and proteins can occur in
many different conformations. The influences leading to cer-
tain types of secondary structures can be divided into the
groups of intra- and intermolecular interactions. In the case of
peptides the sequence, chain length and kind of termini are
examples for the intrinsic properties that determine the struc-
ture. In order to analyze these properties without the influence
of an environment molecular beam experiments on isolated
species can be used as a starting point. If the peptide contains
one of the three aromatic amino acids (phenylalanine, trypto-
phan, tyrosine) resonant two photon ionization (R2PI) and
fluorescence spectroscopy have been shown to be excellent
tools in analyzing species in the gas phase.1–3 Since vibrational
frequencies are sensitive for different back-bone orientations
of peptides, direct structural information can be obtained by
recording IR spectra. Thus IR/UV double resonance spectro-
scopy and especially the IR/R2PI (infrared/resonant 2-photon
ionization)4 method is very powerful for determining and
discriminating between different structures because it is mass-
and isomer-selective.
In the case of the three residue system of two alanines and
one phenylalanine for all possible sequences (Ac–Ala–
Ala–Phe-NH2, Ac–Phe–Ala–Ala-NH2 and Ac–Ala–Phe–
Ala-NH2) only one main conformer20 is observed which al-
ways contains structural elements of the corresponding smaller
system Ac–Ala–Phe–NH2 and Ac–Phe–Ala–NH2.14 A com-
bined g-turn/b-turn, a combined bL/g-turn/g-turn structure or
the combination of b-turns describing a model for a 310 helix
are assigned. For the tripeptides Trp–Gly–Gly11,15 and
Phe–Gly–Gly21 two and four conformers have been found
with similar structures for the global minima of both species.
These structures are assigned to a folded isomer where the
unprotected C- and N-termini are nearby. In the case of
Trp–Gly–Gly the second observed isomer has a stretched
backbone with a free carboxylic group but the NH2 group is
folded back to form a hydrogen bond. This behaviour is
typical for polar end groups.
A polypeptide that is protected at both termini like
Ac–Leu–Val–Tyr(Me)–NHMe (cf. Fig. 1) could serve as a
model for a small part of a protein where certain compounds
in a strand are not influenced by the polar end groups.
Therefore we have extended our investigations on
Ac–Val–Tyr(Me)–NHMe in adding the amino acid leu-
cine to form the tetrapeptide model Ac–Leu–Val–
Tyr(Me)–NHMe. Although leucine is part of several b-sheet
arrangements it also acts as a strong helix former. So it is very
interesting to investigate the influence of this residue on the
rest of the peptide. To our knowledge this is the first investiga-
tion on a tripeptide with three different residues by applying
IR/R2PI spectroscopy. The chosen system will also be of
interest since the sequence Leu–Val–Tyr is similar to the
LVF (leucine valine phenylalanine) sequence of KLVFF which
is part of b-sheets that are considered to be important in the
formation of Alzheimer’s disease. Here the KLVFF peptide
sequence is involved in a process of molecular recognition.
Due to the larger absorption cross section of tyrosine we
Nowadays there are several IR data available on neutral
protected amino acids,5–9,16 dipeptides7,10–15,17,18 and tripep-
tides or tripeptide models.11,12,15,19–22,28 All of the aforemen-
tioned investigated species except for those in ref. 16 and
28 contain one of the aromatic amino acids phenylala-
nine,6–8,10,13–15,17–22 tryptophan5,9,11,15 or tyrosine.12,22 In our
publications12,22 on the tripeptide model Ac–Val–
Tyr(Me)–NHMe we assigned its structure to a b-sheet related
arrangement but a b-turn structure could not be excluded. The
question arises what will happen if the peptide is elongated by
another amino acid and if it is possible to make an unambig-
a Heinrich-Heine Universitat Dusseldorf, Institut fur Physikalische
¨
Chemie I, Universitatsstraße 26.33.O2, 40225 Dusseldorf, and TU
¨
¨
¨
Kaiserslautern, Fachbereich Chemie, Erwin-Schrodingerstr. 52, 67633
¨
¨
Kaiserslautern, Germany. E-mail: gerhards@chemie.uni-kl.de
¨
b Fachbereich Chemie, Philipps-Universitat Marburg, Hans-Meerwein-
Str., 35032 Marburg, Germany
c Universitat Duisburg-Essen, Fachbereich Chemie, Institut fur
Organische Chemie, Universitatsstrasse 5, 45117 Essen, Germany
¨
¨
¨
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4592 | Phys. Chem. Chem. Phys., 2007, 9, 4592–4597

(Lumonics HY 400), was used for excitation to the S1 state and
for ionization. The IR light in the region of 2.84–3.08 mm
(3250–3520 cmÀ1) was generated with a LiNbO3 crystal by
difference frequency mixing of the fundamental (1064 nm) of a
seeded Nd:YAG laser (Spectra-Physics PRO-230) and the
output of a dye laser (Sirah, Precision Scan) pumped by the
second harmonic (532 nm) of the same Nd:YAG laser. The IR
output is amplified by an optical parametric amplification (in a
LiNbO3 crystal) of the output of the IR laser (2.84–3.08 mm)
and the fundamental of the Nd:YAG laser.
Since the time delay chosen for the two lasers is not longer
than 100 ns, all lasers have been spatially overlapped. In order
to obtain IR/R2PI spectra the IR laser is fired 60 ns prior to
the UV laser. The substance (Ac–Leu–Val–Tyr(Me)–NHMe)
and the valve are heated to 170 1C. Helium was used as carrier
gas (2000 mbar).
Fig.
1
Schematic
picture
of
the
tetrapeptide
model
Ac–Leu–Val–Tyr(Me)–NHMe. The angles describing the backbone
(f and c) and part of the side-chain (w1 ) are given for the Tyr residue.
III. Results and discussion
choose the sequence LVY instead of LVF. Tyr(Me) deviates
from Phe only by an OMe group in the aromatic side-chain.
The R2PI spectrum of Ac–Leu–Val–Tyr(Me)–NHMe has
been recorded in the range from 35 300–36 000 cmÀ1 yielding
a broadened unstructured transition with two maxima at
35 578 cmÀ1 and 35 624 cmÀ1. The IR/R2PI spectra recorded
via the transitions at 35 578 and 35 624 cmÀ1 show well
resolved IR transitions but the spectra are not identical. Thus
two isomers of Ac–Leu–Val–Tyr(Me)–NHMe have to be
discussed.
II. Experimental
(a) Synthesis of Ac–Leu–Val–Tyr(Me)–NHMe
This peptide was synthesized as an extension of the tripeptide
model Ac–Val–Tyr(Me)–NHMe already presented before.12
Similarly, N-tert-butyloxycarbonyl-O-methyl-(S)-tyrosine (295
mg, 1.00 mmol) was first converted into its N-methyl amide
after activation with CDI and subsequent treatment with
methylamine in THF (250 mg, 0.81 mmol, 81%). After Boc
deprotection with dry TFA (5 mL) in dichloromethane and
evaporation of the solvent, the free ammonium salt was ob-
tained in quantitative yield. 322 mg (1.00 mmol) of this was
coupled to N-Boc-(S)-valine using HATU/HOAt and lutidine in
dichloromethane–DMF and produced, after aqueous workup,
filtration and drying Boc–Val–Tyr(Me)NHMe (453 mg,
0.45 mmol, 53%). Boc deprotection was accomplished as before
by stirring the starting material at 0 1C in a mixture of
trifluoroacetic acid (5 mL) and dichloromethane (20 mL) for
4 h. After evaporation to 3 mL, the corresponding pure
trifluoroacetate ammonium salt was precipitated by careful
addition of cold dry diethylether (50 mL) in almost quantitative
yield. This was finally coupled to N-acetyl-leucine (62 mg,
0.44 mmol) with HATU/HOAt and lutidine in dichloro-
methane–DMF and furnished, after the usual workup, 99 mg
(0.22 mmol, 50%) of the desired tetrapeptide model N-acetyl-
(S)-leucinyl-(S)-valinyl-(S)-O-methyltyrosinyl-N-methylamide
[abbreviated as Ac–Leu–Val–Tyr(Me)NHMe] was obtained as
a colorless solid.
The IR spectrum of the first isomer (cf. Fig. 2) has been
recorded via the electronic transition at 35 578 cmÀ1. By taking
into account that hydrogen-bonded NH groups are usually
located below 3400 cmÀ1 and free NH groups have frequencies
above 3400 cmÀ1, the four observed IR frequencies of the first
isomer can be divided in two groups: strongly bounded NH
groups at 3357 and 3378 cmÀ1 and weakly bounded or free
NH groups at 3418 and 3469 cmÀ1. Thus the isomer must have
at least two hydrogen bonds and one free NH group.
In comparison with this isomer the IR spectrum of the
second isomer (cf. Fig. 3) looks completely different in the
region below 3400 cmÀ1. Only one very broad transition can
be observed which is centred at 3319 cmÀ1. The frequencies of
3417 and 3471 cmÀ1 are very similar to the frequencies of the
first isomer at 3418 and 3469 cmÀ1, but a third new band is
observed at 3435 cmÀ1
.
In order to assign the isomers to distinct structures, calcula-
tions have been performed at various levels of theory with
increasing accuracy. As a starting point to explore the poten-
tial energy surface a combined molecular mechanics/molecular
dynamics approach has been applied using the class II force
field CFF of Accelrys.8,24 2079 structures have been obtained
at this level of theory. The following ab initio and DFT
calculations have been performed using the Gaussian03 pro-
gram package.25 The 164 most stable structures from the force
field analysis up to 24 kJ molÀ1 above the minimum structure
have been further optimised at the HF/3-21G* level. At this
level of theory the highest relative energy is 51.1 kJ molÀ1
(4276 cmÀ1) with respect to the minimum structure. 27 of these
structures, the five most stable ones, which are all combined
g/b-turns, and the most stable ones for other types of second-
ary structure binding motifs have been reoptimised and
(b) Experimental set-up
The experimental set-up has been described elsewhere (cf. ref. 6
and 23). Thus only a short description is given: the R2PI and IR/
R2PI spectra were measured in a vacuum system consisting of a
differentially pumped linear time-of-flight mass spectrometer
and a pulsed valve (General Valve Iota One, 500 mm orifice)
for skimmed jet expansion (X/D = 130). A frequency-doubled
dye laser (Lumonics HD 300), pumped by a Nd:YAG laser
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Fig. 2 IR/R2PI spectrum of isomer I in the range from 3300–3500 cmÀ1 recorded via the electronic transition at 35 578 cmÀ1. The calculated
harmonic frequencies of the assigned conformer are shown in the lower part and a schematic picture is depicted on the right side, too. The
frequencies obtained from B3LYP/6-31+G* calculations have been scaled with 0.9605.12
harmonic frequencies have been calculated at the B3LYP/6-
31+G* level. Due to the fact that the recorded IR spectra
yield the information that for both isomers at least one NH
group is involved in a hydrogen bond, the other selected
isomers besides the five most stable ones represent different
types of secondary structure binding motifs which contain at
least one hydrogen bond. These types are: double b-turn
(310 helix), single g-turn, double g-turn, and triple g-turn (27
ribbon) arrangements. For comparison extended b-sheet re-
lated structures have also been calculated. Surprisingly, no
single b-turn has been found among the 966 most stable force
field structures. Finally, single point calculations at the MP2/
6-311+G* level have been performed on the structures
optimised at the B3LYP/6-31+G* level. The geometries
Fig. 3 IR/R2PI spectrum of the second isomer recorded via the electronic transition at 35 624 cmÀ1. The scaled frequencies (B3LYP/6-31+G*,
f = 0.960512) of the two g–b conformers which fit best to the experimental data are also shown in the lower trace. A schematic picture of this
structure type is shown on the right side.
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4594 | Phys. Chem. Chem. Phys., 2007, 9, 4592–4597

according to the peptide nomenclature, relative energies and
harmonic frequencies are listed in Table 1 for the most stable
isomers of the aforementioned types of secondary structures.
Some of the calculated structures are shown in Fig. 4. As
reported in earlier papers the Greek letters refer to different
backbone arrangements according to the Ramachandran
plot26,27 defined by the angles f and c (cf. Fig. 1). The
abbreviations a, g+, gÀ describe different positions of the
side-chain defined by the angle w1. In the case of tyrosine
(Tyr(Me)) the additional suffix Æ (cf. Table 1) describes the
position of the OMe group which can be rotated by 1801 with
respect to the C–O axis between the aromatic chromophore
and the O of the OMe group.
Interestingly, the relative energies of all conformers listed
in Table 1 except the combined g–b-turns become much
higher when going from the DFT to the MP2 level. Due to
the lack of optimisation at the MP2 level, dispersion interac-
tion which is not involved in DFT calculations can be over-
estimated. This phenomenon has also been observed recently
by Compagnon et al.28 in the investigation on Z–Aib–
Pro–NHMe. In this work b-turns are the most stable struc-
tures, too. Nevertheless, from the IR data these structures
could be excluded. In a very recent work van Mourik et al.29
reported on the sensitivity of flexible molecules concerning
their conformation and relative stability to the type of electron
correlation used in calculations. They concluded that large
basis sets are needed to circumvent intramolecular basis set
superposition errors which can cause large energy shifts in
MP2 calculations.
Fig. 4 Calculated structures of Ac–Leu–Val–Tyr(Me)–NHMe at the
B3LYP/6-31+G* level of theory according to the nomenclature of
Table 1. The most stable isomers are shown for the following
secondary structure types: g–b-turns, b-sheet related, triple g-turn
and double g-turn. The two corresponding structures of the experi-
mentally observed isomers I and II are marked with frames.
The IR/R2PI spectrum of isomer I shows two strong
transitions at 3378 and 3357 cmÀ1 that can be related to two
strongly hydrogen-bonded NH groups. This may lead to the
conclusion that this is due to a conformer with a double-
g-turn. Nevertheless, the vibrational patterns predicted for the
three different types of double g-turns (b–g–g; g–b–g; g–g–b)
are not in good agreement to the experimental spectrum. The
best agreement for these types of structures is obtained for
However, it can be concluded that with respect to the DFT
calculations several structural arrangements of similar energy
have to be discussed. b-Sheet related structures as well as
combined g-turn/b-turns and triple g-turns structures may be
formed. Since the two experimentally observed IR spectra
show at least one IR transition that is located significantly
below 3400 cmÀ1 a completely b-sheet related structure like in
Ac–Val–Phe–OMe or Ac–Val–Tyr(Me)–NHMe can be ex-
cluded, i.e. in a b-sheet related structure only free NH stretch-
ing frequencies can be observed.
isomer 10 (b–g–g). The frequencies calculated for the NHVal,
NHTyr, and NHMe stretching modes fit very well to the
experimental values but the frequency predicted for the NHLeu
group deviates by 24 cmÀ1 (cf. Table 1). The Leu residue is in a
bL conformation and it should be pointed out that for this type
of structure in an Ac–X (X = amino acid) binding motif, the
NH stretching vibration is usually located at about 3440 cmÀ1
,
e.g. in Ac–Phe–NHMe,8 Ac–Trp–NHMe,5 Ac–Val–Phe–
OMe10 or Ac–Val–Tyr(Me)–NHMe12 the corresponding NH
stretching vibrations of Phe, Trp, and Val deviate only a few
Table 1 Relative energies (including zero point energies) and scaled harmonic frequencies (scaling factor: 0.9605 12) at the DFT level of theory
using the B3LYP functional and the 6-31+G* basis set. Intensities are given in km molÀ1. Single point MP2 energies have been calculated at the
DFT optimised structures using the 6-311+G* basis set. Frequencies of assigned isomers are given in bold letters
Geometries
Rel. energies/kJ molÀ1
Calculated vibrations [cmÀ1] and intensities [km molÀ1
]
Isomer Conformation
Secondary structure DFT
SP-MP2
NH-Leu
NH-Val
NH-Tyr
NHMe
1
2
3
4
5
6
7
8
gL(gÀ)aL(gÀ)gL(g+)+ g-turn-b-turn
0
1.55
5.57
6.16
0.92
36.87
37.33
0
33.23
10.44
41.65
40.08
41.69
34.57
40.73
40.04
3469(25)
3438(62)
3468(23)
3478(23)
3468(21)
3488(30)
3465(23)
3467(21)
3468(22)
3442(52)
3440(79)
3439(82)
3353(141)
3426(86)
3362(151)
3302(227)
3348(230)
3487(29)
3448(49)
3423(22)
3378(120)
3470(35)
3427(47)
3472(31)
3456(44)
3416(98)
3382(110)
3460(38)
3428(137)
3393(202)
3416(92)
3425(163)
3357(125)
3351(158)
3456(37)
3371(90)
3417(230)
3468(50)
3393(114)
3408(270)
3368(128)
3424(186)
3469(48)
3361(208)
3475(25)
3383(146)
3392(149)
3469(32)
bL(a)bL(g+)bL(a)+
gL(gÀ)gL(a)gL(a)+
b-sheet related
Triple g-turn
gD(gÀ)aL(gÀ)gL(g+)À g-turn-b-turn
gL(gÀ)gL(a)gL(g+)+ Triple g-turn
eD(gÀ)aL(gÀ)gL(gÀ)+ Double b-turn
8.72
11.08
12.53
12.86
12.99
14.50
14.62
22.50
gL(a)gL(gÀ)bL(a)+
Single g-turn
gL(gÀ)bL(gÀ)gL(g+)+ Double g-turn
gL(gÀ)gL(gÀ)bL(a)À Double g-turn
bL(gÀ)gL(gÀ)gL(gÀ)+ Double g-turn
bL(g+)bL(gÀ)gL(gÀ)+ Single g-turn
bL(g+)gL(gÀ)bL(a)+ Single g-turn
9
10
11
12
Experimental vibrations
Isomer I (assigned to isomer 5) 3469
Isomer II (assigned to isomer 4) 3471
3357
3319
3418
3435
3378
3417
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wavenumbers from 3440 cmÀ1. The band position of 3442
cmÀ1 calculated for the NHLeu stretching mode in the bL
conformation is therefore in good agreement with the expected
value for this binding motif, but it is not in agreement with the
called 27 ribbon motif, which is a special helical type consisting
of consecutive seven membered rings.
While a triple g-turn arrangement is predicted for isomer I,
the experimentally observed frequencies of isomer II (cf. Fig.
3) fit best to a combined g–b-turn structure. Two isomers
(1 and 4) of this type belong to the most stable structures
(cf. Table 1). Both isomers contain a b-turn type I arrange-
ment30 similar to the one assigned for Ac–Ala–
Ala–Phe–NH2.20 This tripeptide exhibits similar frequencies
as the ones observed for isomer II of Ac–Leu–Val–Tyr(Me)–
NHMe. The calculated structures of isomers 1 and 4 of
Ac–Leu–Val–Tyr(Me)–NHMe differ only by the orientation
of the leucine residue which is gD in isomer 4 and gL in isomer
1, representing the reverse and classical g-turn. (Note: The
abbreviations gD and gL refer to different arrangements with
respect to the Ramachandran plot,26 D and L should not be
mixed up with the absolute configuration of the Ca atom
which is always S.) For the transition of lowest frequency
centered at 3319 cmÀ1, the calculated NH stretching frequency
of the valine moiety fits better to isomer 4 (3302 cmÀ1) than to
isomer 1 (3353 cmÀ1). The three other NH stretching frequen-
cies calculated for both isomers have similar values which
deviate by not more than 9 cmÀ1 from each other. The
transition with the lowest frequency at 3417 cmÀ1 is assigned
to the NHMe protection group which is involved in the
hydrogen bond formed within the b-turn. The transitions at
3435 and 3471 cmÀ1 can only be assigned to the free NH
groups of the tyrosine and leucine residues. The calculated NH
stretching vibration of the tyrosine residue shows the strongest
deviation from the experimental values. In both isomers 1 and
4 the calculated frequency is too high. This deviation which
has also been observed for other calculated b-turn structures
using the B3LYP/6-31+G* method20 might be an under-
estimation of the p-interaction with the carbonyl group of
the amide bond. Other conformers with a single g-turn are
either energetically much less favoured or show no good
agreement with the experimental frequencies, e.g. the red shift
of the bounded NH group is much too small in all cases
experimental value of 3418 cmÀ1
.
Another prominent secondary structure binding motif, the
double b-turn (310 helix), can be excluded due to its vibrational
pattern which is quite different from the experimental IR
spectrum (cf. Table 1).
By comparing the calculated harmonic frequencies with the
experimental values obtained for isomer I by far the best fit is
obtained for isomer 5 (cf. Fig. 2). This isomer adopts a triple
g-turn (gL(gÀ)gL(a)gL(g+)+) arrangement in which the mid-
dle residue, valine, is not so strongly folded like the two outer
residues leucine and tyrosine. This is indicated by the long
distance of 2.91 A (calculated at the DFT level) between the
carbonyl group of leucine and the NH group of tyrosine. Thus
only a very weak interaction is possible, leading to a relatively
high NH stretching frequency of 3418 cmÀ1 that is well
predicted by the DFT calculations (3428 cmÀ1). Furthermore
the N–HÁ Á ÁO angle of the intramolecular hydrogen-bond is
only 1101. For comparison, the two NH groups of isomer 5
that are strongly hydrogen-bonded to the carbonyl groups of
valine and the acetyl group have distances of 1.97 and 2.12 A
and N–HÁ Á ÁO angles of 1501 and 1391, respectively. This leads
to strong red shifts of the NH stretching frequencies to 3378
and 3357 cmÀ1 which are also well predicted by the DFT
calculations (3368 and 3348 cmÀ1). Saturation effects due to
large IR power cannot be completely excluded and may have
an influence on the shape of the bands, nevertheless the
calculated intensities reproduce the order and magnitude of
the experimental bands in which free and hydrogen bonded
species can clearly be distinguished by their different band-
widths.
All hydrogen bond distances and angles are listed in Table
2. To our knowledge Ac–Leu–Val–Tyr(Me)–NHMe is the first
species investigated up to now that forms a triple g-turn
structure. This secondary structure element contains the so-
Table 2 Distances and angles calculated at B3LYP/6-31+G* level of theory for two different types of hydrogen bonding: C10 for b-turns and C7
for g-turns. The isomers represent the structures: g-turn/b-turn (isomers 1 and 4), triple g-turns (3, 5) and double g-turns (8, 9, 10). The indices of
the atoms correspond to the nomenclature depicted in Fig. 1. Additionally the calculated NH stretching frequencies are given for every isomer,
according to Table 1
Type of hydrogen bonding
C10 (b-turn)
r/A
C7 (g-turn)
r/A
+/1
Freq./cmÀ1
3417
+/1
Freq./cmÀ1
Isomer
1
3
N4H4Á Á ÁO2QC2
2.13
2.08
N4–H4–O2
159.7
158.5
N2H2Á Á ÁO1QC1
N2H2Á Á ÁO1QC1
N3H3Á Á ÁO2QC2
N4H4Á Á ÁO3QC3
N2H2Á Á ÁO1QC1
N2H2Á Á ÁO1QC1
N3H3Á Á ÁO2QC2
N4H4Á Á ÁO3QC3
N2H2Á Á ÁO1QC1
N4H4Á Á ÁO3QC3
N2H2Á Á ÁO1QC1
N3H3Á Á ÁO2QC2
N3H3Á Á ÁO2QC2
N4H4Á Á ÁO3QC3
2.08
2.1
2.17
2.14
1.9
2.12
2.91
1.97
2.37
2
2.12
2.14
2.06
2.04
N2–H2–O1
N2–H2–O1
N4–H4–O2
N4–H4–O3
N2–H2–O1
N2–H2–O1
N3–H3–O2
N4–H4–O3
N2–H2–O1
N4–H4–O3
N2–H2–O1
N3–H3–O2
N3–H3–O2
N4–H4–O3
143.6
140.9
136.4
140.2
152.6
139.4
110.9
150
128.1
148.3
141.5
141.1
144
3353
3362
3382
3393
3302
3348
3428
3368
3423
3361
3378
3357
3351
3383
4
5
N4H4Á Á ÁO2QC2
N4–H4–O2
3408
8
9
10
142.9
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4596 | Phys. Chem. Chem. Phys., 2007, 9, 4592–4597

(cf. Table 1). Thus only a g–b-turn arrangement, most prob-
ably a gD(gÀ)aL(gÀ)gL(g+)À (isomer 4), can be predicted for
the second isomer of Ac–Leu–Val–Tyr(Me)–NHMe. It should
also be mentioned that the g–b-turn arrangement is the most
stable structure both at the DFT level as well as on all
calculated levels of ab initio theory (HF, MP2). For the sake
of comparison the stick spectra of both isomers 1 and 4, which
are possible candidates for isomer II, are depicted in Fig. 3.
10 C. Unterberg, A. Gerlach, T. Schrader and M. Gerhards, J. Chem.
Phys., 2003, 118(18), 8296.
11 I. Hunig and K. Kleinermanns, Phys. Chem. Chem. Phys., 2004, 6,
¨
2650.
12 H. Fricke, A. Gerlach, C. Unterberg, P. Rzepecki, T. Schrader and
M. Gerhards, Phys. Chem. Chem. Phys., 2004, 6, 4636.
13 W. Chin, J.-P. Dognon, F. Piuzzi, B. Tardivel, I. Dimicoli and M.
Mons, J. Am. Chem. Soc., 2005, 127, 707.
14 (a) W. Chin, J.-P. Dognon, C. Canuel, F. Piuzzi, I. Dimicoli,
M. Mons, I. Compagnon, G. von Helden and G. Meijer,
J. Chem. Phys., 2005, 122, 054317; (b) W. Chin, F. Piuzzi, J.-P.
Dognon, I. Dimicoli and M. Mons, J. Chem. Phys., 2005, 123,
084301.
IV. Conclusion
15 J. M. Bakker, C. Plutzer, I. Hunig, T. Haber, I. Compagnon, G.
¨
¨
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von Helden, G. Meijer and K. Kleinermanns, ChemPhysChem,
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22 M. Gerhards, Spectroscopy of neutral peptides in the gas phase –
structure, reactivity, microsolvation, molecular recognition, , in
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The tetrapeptide model Ac–Leu–Val–Tyr(Me)–NHMe has
been investigated in the gas phase by applying IR/R2PI
spectroscopy. Two isomers have been observed and the struc-
tures have been assigned by comparison with theoretical
results. None of the isomers has a stretched backbone and it
turns out that the extension of the smaller Ac–Val–
Tyr(Me)–NHMe by the amino acid leucine leads to a strong
preference of folded isomers. One isomer contains two hydro-
gen bonds by forming a combined g-turn/b-turn arrangement.
In the case of the second isomer a triple g-turn arrangement
(27 ribbon) can be observed for the first time. Both isomers
have in common that the leucine residue adopts a g-turn.
Further investigations will show if the dimer of Ac–Leu–Val–
Tyr(Me)–NHMe forms a b-sheet arrangement similar to the
dimer of Ac–Val–Tyr(Me)–NHMe.31
23 C. Unterberg, A. Jansen and M. Gerhards, J. Chem. Phys., 2000,
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Acknowledgements
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The authors thank the Deutsche Forschungsgemeinschaft
(DFG) for financial support and the ‘‘Rechenzentren der
Heinrich-Heine-Universitat Dusseldorf’’ and especially the
¨
‘‘Universitat zu Koln’’ for the granted computer time. This
¨
¨
work is part of the PhD thesis of H.F.
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