A hybrid foldamer with unique architecture from conformationally constrained aliphatic-aromatic amino acid conjugate

Article abstract of DOI:10.1016/j.tet.2006.08.032

In this paper, we describe the design and synthesis of a novel hybrid foldamer, derived from a conformationally constrained aliphatic-aromatic amino acid conjugate that adopts a well-defined, compact, three-dimensional structure, governed by a combined co

Full text of DOI:10.1016/j.tet.2006.08.032

Tetrahedron 62 (2006) 10141–10146
A hybrid foldamer with unique architecture from
conformationally constrained aliphatic–aromatic
amino acid conjugate
Deekonda Srinivas,a Rajesh Gonnade,b Sapna Ravindranathanc and Gangadhar J. Sanjayana,
*
aDivision of Organic Synthesis, National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411 008, India
bCenter for Materials Characterization, National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411 008, India
cCentral NMR Facility, National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411 008, India
Received 15 May 2006; revised 27 July 2006; accepted 10 August 2006
Available online 6 September 2006
Abstract—In this paper, we describe the design and synthesis of a novel hybrid foldamer, derived from a conformationally constrained
aliphatic–aromatic amino acid conjugate that adopts a well-defined, compact, three-dimensional structure, governed by a combined
conformational restriction imposed by the individual amino acids from which the foldamer is composed. Conformational investigations
confirmed the prevalence of a unique doubly bent conformation for the foldamer, in both solid and solution states, as evidenced from single
crystal X-ray and 2D NOESY studies, respectively. The findings suggest that constrained aliphatic–aromatic amino acid conjugates offer new
avenues for the de novo design of hybrid foldamers with distinctive structural architectures. Furthermore, the de novo design strategy
disclosed herein has the potential for significantly augmenting the ‘tool-box’ of the modern day peptidomimetic chemist, as well as providing
a novel approach to the field of rational design.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
2. Design principles
Foldamers1 as a class of conformationally ordered synthetic
oligomers have been ushered into prominence primarily due
to their enormous potential for the creation of unnatural
oligomers that adopt discrete tertiary structures, just as
biopolymers. The compact conformational features and their
adjustable lengths mean that these synthetic oligomers may
provide excellent starting points for the elaboration of
protein mimics that might be difficult to design based on
small-molecule scaffolds. Extensive investigations by sev-
eral groups have resulted in the generation of a myriad of
such synthetic oligomers with diverse backbone structures,
conformations,2 and functions.3 Of late, increasing attention
is being devoted to the design and development of hybrid
foldamers with a view to expanding the conformational
space available for foldamer design.4–6 Of particular interest
are a,b-hybrid peptides, reported by Gellman’s group,4
composed of alternately changing a- and b-amino acid
constituents. NMR studies provided convincing hints for
the formation of special helix types in this novel foldamer
class.
In an effort to augment the repertoire of conformational
space available for foldamer design, we set out to generate
novel foldamers, which contain conformationally con-
strained a-amino acid–aromatic amino acid-conjugated
building blocks as subunits. In this article, we describe the
design, synthesis, and conformational studies of a novel
hybrid foldamer 3, derived from regularly repeating
a-aminoisobutyric acid (Aib) and 3-amino-4,6-dimethoxy-
benzoic acid (Adb) residues (Aib-Adb motif). We designed
the Aib-Adb motif-based foldamer 3 anticipating that the
corresponding oligomers would adopt a well-defined, com-
pact, three-dimensional structure, governed by a combined
conformational restriction imposed by both Aib and Adb
residues (highlighted in blue and red bold bonds in 3,
Scheme 1). The achiral Aib residue is known to play a key
role7 in the conformational restriction of polypeptides due
to its overwhelmingly constrained phi (fꢀ60ꢁ) and psi
(cꢀ30ꢁ), while the backbone-rigidified aromatic amino
acid residue Adb8 is known to induce a crescent conforma-
tion in its oligomers via localized five- and six-membered
ring hydrogen bonding interactions. Thus, we reasoned
that hetero-oligomers made of Aib-Adb repeat motif should
also display conformational rigidity. Structural studies (vide
infra) indeed showed that the Aib-Adb dimer 3 folds into
a well-defined, compact, three-dimensional structure, as evi-
denced from single crystal X-ray and 2D NOESY studies.
Keywords: Foldamer; Amino acids; Peptidomimetics; Conformation.
* Corresponding author. Tel.: +91 20 25902082; fax: +91 20 25893153;
e-mail: gj.sanjayan@ncl.res.in
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.08.032

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D. Srinivas et al. / Tetrahedron 62 (2006) 10141–10146
Most astonishingly, the crystal structure analysis revealed
a fascinating arrangement of water clusters, in the crystal
lattice, held by the backbone amide groups of the foldamer
with a peculiar architecture. It is noteworthy that the under-
standing of three-dimensional structures of water clusters
has profound implications in several areas ranging from
water-mediated molecular self-assembly9 to protein struc-
ture and function.10 Furthermore, exploration of conforma-
tionally ordered synthetic oligomers that interact with
water molecules may enable better understanding of the
much debated issue of water interaction with Anti Freeze
Proteins (AFPs) and Anti Freeze Glyco Proteins (AFGPs).11
Figure 1. Crystal structure of the Aib-Adb motif-based foldamer 3. Water
molecules in the unit cell are represented in spheres, for aiding quick iden-
tification. Color coding: C green, H gray, N blue, O red.
3, containing alternately changing Aib and Adb residues,
shows an entirely different structural architecture, a fact
that clearly attests the importance of hybrid foldamer strat-
egy4 for augmenting the conformational space available
for novel foldamer design.
Investigation of the crystal structure of 3 revealed the
presence of water molecules embedded in the crystal lattice.
A detailed analysis of the arrangement of water molecules
revealed highly interesting features (Fig. 2).
There are mainly two types of water molecules discernible in
the crystal lattice: the first type (colored red) forms a poly-
meric chain of water clusters and the second type (colored
orange) bridges adjacent foldamer molecules as well as con-
nects the foldamer to the water clusters, eventually forming
a complex three-dimensional hydrogen bonded network. All
the backbone carbonyl oxygens of the foldamer are involved
in strong hydrogen bonding interactions with water mole-
Scheme 1. Synthesis of 3: Reagents and conditions: (i) Boc-Aib-OH,
DIPEA, TBTU, MeCN, rt, 6 h; (ii) dry HCl (gas), dioxane, rt, 5 min; (iii)
2 N LiOH, MeOH, rt, 12 h; (iv) DIPEA, TBTU, MeCN, rt, 8 h; (v) metha-
nolic MeNH2, 48 h, rt. Note: for aiding quick identification, the conforma-
tional restriction imposed by both Aib and Adb residues in 3 is highlighted
in blue and red bold bonds, respectively.
3. Results and discussion
13
˚
cules (O/O<3.0 A). However, only the Aib amide NHs
(N3H and N5H) partake in interactions with water mole-
cules, leaving the Adb amide NHs (N2H and N4H) and the
methyl amide NH (N1H) to be satisfied with S(5)- and
S(6)-type14 hydrogen bonding interactions, respectively.
The Aib-Adb motif-based foldamer 3 was assembled from
Boc-Aib-Adb-OMe building block 2a, which in turn was
synthesized by coupling the protected amino acids Aib and
Adb using TBTU as a coupling agent (Scheme 1). However,
attempts to synthesize higher oligomers using this ‘segment
doubling strategy’ were unsuccessful, due to the formation
of intractable mixture of products under various conditions.
The foldamer 3 crystallized from acetonitrile/water (90:10)
in triclinic space group P-1. The unit cell contained two
foldamers and 14 water molecules (Fig. 1).
Investigation of the crystal structure revealed that the intrin-
sically constrained Aib residues imposed a significant twist
on the foldamer backbone, as expected, with f and c torsion
angles close to 60 and 30ꢁ, respectively, forcing the foldamer
backbone to adopt a doubly bent conformation. It is interest-
ing to compare the conformational propensities of the homo-
oligomers made of the individual amino acids (Aib and Adb)
and their hybrid oligomer 3. Whereas the homo-oligomers of
Aib and Adb have been reported to adopt 310-helical12 and
crescent architectures,8 respectively, the hybrid foldamer
Figure 2. Crystal structure of Aib-Adb motif-based foldamer 3 showing
interaction of the foldamer backbone with water molecules.

D. Srinivas et al. / Tetrahedron 62 (2006) 10141–10146
10143
The water molecules, in pairs (colored orange), that bridge
the backbone carbonyls of the adjacent residues donate
two hydrogen bonds to the backbone carbonyl oxygens of
the foldamer forming 12-membered ring hydrogen bonded
network. Further, these water pairs accept hydrogen bonds
(one each) from the Aib NHs of the adjacent foldamers.
The backbone carbonyls O1 and O10 keep the parallel
running water chains in place by hydrogen bonding with
the water molecule (O14W) that is part of the centrosymmet-
ric six-membered water cluster. Interestingly, the same water
molecule (O14W) helps in building the hydrogen bonded
three-dimensional network by donating a hydrogen bond
to the carbonyl oxygens (O1 and O10) of another foldamer.
in solution state could not be verified. One of the most
characteristic NOE interactions that can be anticipated for
a doubly bent conformation for 3, as observed in the solid
state, would be the NH versus NH dipolar couplings of the
amide NHs of the adjacent Aib-Adb residues. Analysis of
the 2D NOESY data (500 MHz, CDCl3) indeed revealed
the existence of NH versus NH dipolar couplings of the
adjacent Aib-Adb residues (NH1/NH2 and NH3/NH4) as
anticipated (Fig. 4). Furthermore, the characteristic NOE
interactions between amide NH and the adjacent O-aryloxy-
methyls in 3 (NH2/OMe1, NH3/OMe2, NH4/OMe3,
and NH5/OMe4) also strongly suggest their syn orienta-
tion, thereby making space for the S(5) and S(6)14 type
hydrogen bonded arrangement, a common feature in
O-alkoxy arylamides.8
The infinite chain of water clusters has alternate four- and
six-membered rings (oxygen atoms) sharing one edge. The
oxygen atoms of the water molecules in four-membered
rings assume square planar structure and the six-membered
rings display a centrosymmetric chair conformation. The
infinite chains of water clusters are held together by strong
Ow–H/Ow hydrogen bonding interactions (Ow/
4. Summary
In summary, we have designed and synthesized a novel con-
strained aliphatic–aromatic conjugated hybrid foldamer that
adopts a well-defined, compact, three-dimensional architec-
ture,16 governed by a combined conformational restriction
imposed by the individual amino acids from which it is com-
posed. Conformational investigations confirmed the preva-
lence of a unique doubly bent conformation for 3, in both
solid and solution states, as evidenced from single crystal
X-ray and 2D NOESY studies, respectively. The findings
suggest that constrained aliphatic–aromatic amino acid
conjugates offer new avenues for the de novo design of
foldamers with distinctive structural architectures. The
most striking feature of the present de novo designed
foldamer is its remarkable ability to stabilize supramolecular
polymeric chain of water clusters held together by strong
hydrogen bonding interactions. We are currently probing
the possibility of water cluster formation in related fol-
damers, as well as investigating the influence of substitution
pattern in the aromatic nuclei on the structural architecture
of the corresponding hybrid foldamer.
13
˚
Ow¼2.73–2.85 A). The supramolecular chains of water
clusters are aligned parallel to each other (Fig. 3).
The folded structure is organized by the backbone H-bonds
in solution state, as evidenced from the FTIR spectroscopy,
a sensitive tool that is easily applicable for the detection of
vibrational modes influenced by the presence of the
H-bonds. In the N–H stretch region of 3, the free N–H vibra-
tion, presumably due to the N-terminal Boc amide NH,
appears as a weak signal at 3419 cmꢂ1, while intramolecular
H-bonded N–H stretches give rise to a broad band in the
region 3388 cmꢂ1. Another important source of information
in IR spectra is the amide carbonyl region (1600–
1700 cmꢂ1). The band at 1647 cmꢂ1 can be ascribed to the
H-bonded carbonyl in the backbone. Weaker H-bonds result
in a slightly increased frequency. The band at 1683 cmꢂ1
could be assigned to the N-terminal Boc carbonyl that is
not taking part in intramolecular H-bonding.
Solution-state NMR studies (500 MHz) of the foldamer 3 in
CDCl3 strongly suggested the prevalence of a doubly bent
conformation in solution state, similar to the one observed
in the solid state, although the existence of water clusters
5. Experimental
5.1. General
Unless otherwise stated, all the chemicals and reagents were
obtained commercially. Acetonitrile was dried by distilling
˚
over calcium hydride and kept it over 4 A molecular sieves,
prior to use. Chromatography was done on pre-coated silica
gel plates (kieselgel 60F254, Merck). Column chromato-
graphic purifications were done with 100–200 mesh silica
gel. NMR spectra were recorded in CDCl3 on Ac
200 MHz or DRX-500 MHz Bruker NMR spectrometers.
All chemical shifts are reported in d ppm downfield to
TMS and peak multiplicities are reported as singlet (s),
doublet (d), quartet (q), broad (br), broad singlet (br s) and
multiplet (m). Elemental analyses were performed on an
Elmentar-Vario-EL (Heraeus Company Ltd, Germany). IR
spectra were recorded in Nujol or CHCl3 using a Shimadzu
FTIR-8400 spectrophotometer. Melting points were deter-
mined on a Buchi Melting Point B 540. MALDI-TOF
mass spectra were obtained from Voyager-PE, Voyager
DEPRO, and Voyager-DE STR Models. Single crystal
Figure 3. Aview of the arrangement of polymeric chain of water clusters in
the crystal lattice of 3. For clarity, the polymeric chains of water clusters are
represented in spheres and the foldamers in lines. Color coding: C green,
H gray, N blue, O red.

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D. Srinivas et al. / Tetrahedron 62 (2006) 10141–10146
Figure 4. Partial 2D NOESY spectra of 3 (500 MHz, CDCl3) showing characteristic NH1/NH2 and NH3/NH4 interactions (see also Supplementary data).
For aiding interpretation of the 2D data, crystal structure of 315 with selected labeled atoms is also shown.
X-ray data were collected on a Bruker SMART APEX
CCD Area diffractometer with graphite monochromatized
157.8, 154.5, 152.6, 123.1, 120.4, 111.3, 95.5, 57.6, 56.4,
55.8, 51.5, 28.1, 25.7; MALDI-TOF Mass: 435.34 (M+K).
Anal. Calcd for C19H28N2O7: C, 57.57; H, 7.07; N, 7.07.
Found: C, 57.37; H, 7.03; N, 6.99.
˚
(Mo Ka¼0.71073 A) radiation at room temperature. All
the data were corrected for Lorentzian, polarization, and
absorption effects using Bruker’s SAINT and SADABS
programs. SHELX-97 was used for structure solution and
full matrix least squares refinement on F2. Hydrogen atoms
were included in the refinement as per the riding model.
5.1.2. 5-(2-Amino-2-methyl-propionylamino)-2,4-di-
methoxy-benzoic acid methyl ester hydrochloride 2b.
To an ice-cold stirred solution of the compound 2a (0.5 g,
1.3 mmol) in dry dioxane (10 ml) was bubbled dry HCl
gas for 5 min. Then dry ether (15 mL) was added to the
reaction mixture, when the amine hydrochloride (2b) precip-
itated out as a white solid (0.37 g, 87%). The solid was
filtered, washed with dry ether, dried, and used for the next
reaction, without further purification.
5.1.1. 5-(2-tert-Butoxycarbonylamino-2-methyl-propio-
nylamino)-2,4-dimethoxy-benzoic acid methyl ester 2a.
To an ice-cold stirred solution of the acid Boc-Aib-OH
(5.70 g, 28.0 mmol, 1 equiv) and the aromatic amine 1
(5.33 g, 25.3 mmol, 0.9 equiv) in dry acetonitrile (30 mL)
was added DIPEA (7.53 mL, 42.1 mmol, 1.5 equiv)
followed by TBTU (12.61 g, 39.3 mmol, 1.4 equiv). The
resulting mixture was stirred for 6 h at room temperature.
The solvent was stripped off under reduced pressure and
the residue was diluted with dichloromethane and washed
sequentially with potassium hydrogen sulfate solution,
saturated sodium bicarbonate, and water. Drying and con-
centration of the DCM extract under reduced pressure
gave the crude product, which on column chromatography
(50% EtOAc/Hexane) afforded the desired pure product 2a
(8 g, 72%). Mp 145 ꢁC; IR (CHCl3) n (cmꢂ1): 3020, 1712,
1531, 1463, 1215, 754; 1H NMR (500 MHz, CDCl3):
d 8.81 (s, 1H), 8.58 (br s, 1H), 6.44 (s, 1H), 5.02 (br s,
1H), 3.87 (s, 3H), 3.85 (s, 3H), 3.78 (s, 3H), 1.52 (s, 6H),
1.38 (s, 9H); 13C NMR (125 MHz, CDCl3): d 172.4, 165.5,
5.1.3. 5-(2-tert-Butoxycarbonylamino-2-methyl-propio-
nylamino)-2,4-dimethoxy-benzoic acid 2c. To a solution
of compound 2a (2.2 g, 5.6 mmol, 1 equiv) in methanol
(15 mL) was added 2 M LiOH solution (11.08 mL,
22.2 mmol, 4 equiv). The reaction mixture was stirred at
room temperature overnight. The reaction mixture was
evaporated to dryness and diluted with distilled water, and
acidified with saturated potassium hydrogen sulfate. Then
the aqueous layer was extracted with ethyl acetate
(2ꢃ100 mL). The combined organic extracts were washed
with brine. Drying and concentration of the organic layer,
under reduced pressure, yielded the desired product 2c
(2.0 g, 94%), which was used for the next reaction, without
further purification.

D. Srinivas et al. / Tetrahedron 62 (2006) 10141–10146
10145
5.1.4. 1-(5-(1-(2,4-Dimethoxy-5-methylcarbonyl-
References and notes
phenylcarbamoyl)-1-methyl-ethylcarbamoyl)-2,4-di-
methoxy-phenylcarbamoyl)-1-methyl-ethyl)-carbamic
acid tert-butyl ester 3. To an ice-cold stirred solution of the
acid 2c (2.0 g, 5.2 mmol, 1 equiv) and amine 2b (1.73 g,
5.23 mmol, 1 equiv) in dry acetonitrile (20 mL) was added
DIPEA (2.3 mL, 13.0 mmol, 2.5 equiv) followed by TBTU
(2.35 g, 7.3 mmol, 1.4 equiv). The resulting reaction mix-
ture was stirred overnight at room temperature. The solvent
was stripped off under reduced pressure; the residue was dis-
solved in dichloromethane (100 mL) and washed sequen-
tially with potassium hydrogen sulfate solution, saturated
sodium bicarbonate, and water. Drying and concentration
in vacuum yielded the crude ester, which was directly used
for the next amidation reaction, without further purification.
The crude ester was taken in an RB flask containing satu-
rated methanolic methylamine solution (25 mL) and stirred
at room temperature for two days. The solvent was removed
under reduced pressure, and the crude product was purified
by column chromatography (5% methanol/ethyl acetate, Rf
0.4) to yield pure 3 (2.0 g, 69%), which could be crystallized
from acetonitrile/water (90:10). Mp 212 ꢁC; IR (CHCl3)
n (cmꢂ1): 3419, 3388, 3018, 1683, 1647, 1610, 1517,
1. For reviews, see: (a) Gellman, S. H. Acc. Chem. Res. 1998, 31,
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Eur. J. Org. Chem. 2004, 17–29; (g) Licini, G.; Prins, L. J.;
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J. Am. Chem. Soc. 2005, 127, 10590–10599; (c) Huck, B. R.;
Gellman, S. H. J. Org. Chem. 2005, 70, 3353–3362; (d)
Goto, K.; Moore, J. S. Org. Lett. 2005, 7, 1683–1686; (e)
Arunkumar, E.; Ajayaghosh, A.; Daub, J. J. Am. Chem. Soc.
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B. L. J. Am. Chem. Soc. 2005, 127, 2637–2640; (g) Violette,
A.; Averlant-Petit, M. C.; Semetey, V.; Hemmerlin, C.;
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D.; Guichard, G. J. Am. Chem. Soc. 2005, 127, 2156–2164;
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Chem. Soc. 2004, 126, 2–3; (b) Sadowsky, J. D.; Schmitt,
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(c) Norgren, A. S.; Arvidsson, P. I. Org. Biomol. Chem. 2005,
3, 1359–1361; (d) Chang, K. J.; Kang, B. N.; Lee, M. H.;
Jeong, K. S. J. Am. Chem. Soc. 2005, 127, 12214–12215.
4. Hayen, A.; Schmitt, M. A.; Ngassa, F. N.; Thomasson, K. A.;
Gellman, S. H. Angew. Chem., Int. Ed. 2004, 43, 505–510.
5. (a) Roy, R. S.; Karle, I. L.; Raghothama, S.; Balaram, P. Proc.
Natl. Acad. Sci. U.S.A. 2004, 101, 16478–16482; (b) Sharma,
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2005, 44, 5878–5882; (c) Baldauf, C.; Gunther, R.; Hofmann,
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1
1215, 758; H NMR (500 MHz, CDCl3): d 8.99 (s, 1H),
8.89 (s, 1H), 8.76 (s, 1H), 8.44 (br s, 1H), 8.26 (s, 1H), 7.53
(s, 1H), 6.46 (s, 1H), 6.38 (s, 1H), 5.07 (br s, 1H), 3.95 (s,
3H), 3.88 (s, 3H), 3.87 (s, 3H), 3.84 (s, 3H), 2.93 (d, 3H,
J¼4.8 Hz), 1.70 (s, 6H), 1.52 (s, 6H), 1.40 (s, 9H); 13C
NMR (125 MHz, CDCl3): d 172.5, 172.1, 165.7, 164.7,
154.6, 152.8, 152.4, 124.6, 124.0, 121.2, 121.1, 114.1,
113.8, 94.9, 94.8, 58.3, 57.5, 56.4, 56.2, 55.9, 28.1, 26.4,
25.5; MALDI-TOF Mass: 681.95 (M+Na). Anal. Calcd for
C32H45N5O10: C, 58.27; H, 6.82; N, 10.62. Found: C,
58.15; H, 6.80; N, 10.59.
5.1.5. Crystal data for 3 C32H45N5O10$7H2O. M¼785.84.
Colorless crystal, approximate size 0.56ꢃ0.27ꢃ0.05 mm,
multi scan data acquisition, q range¼2.12–25.00ꢁ, triclinic,
space group P-1, a¼6.893 (15), b¼15.55 (3), c¼20.21
ꢁ
ꢁ
ꢁ
˚
(4) A, a¼110.27 (5) , b¼93.77 (5) , g¼93.37 (5) , V¼
2019 (8) A , Z¼2, rcalcd¼1.292 gcmꢂ1, T¼297 (2), m (Mo
3
˚
Ka)¼0.105 mmꢂ1, 7052 reflections measured, 4044 unique
[I>2s(I)] reflections, 575 refined parameters, R value
0.0551, wR2¼0.1244 (all data R¼0.0916, wR2¼0.01372).
Crystallographic data of 3 have been deposited with the
Cambridge Crystallographic Data Centre as supplementary
publication no. CCDC-289024. Copies of the data can be
obtained free of charge on application to CCDC, 12 Union
Road, Cambridge CB21EZ, UK.
6. Cyclic peptides containing proline-aromatic amino acid units
have been reported by Kubik et al., see: (a) Otto, S.; Kubik,
S. J. Am. Chem. Soc. 2003, 125, 7804–7805; (b) Heinrichs,
G.; Kubik, S.; Lacour, J.; Vial, L. J. Org. Chem. 2005, 70,
4498–4501.
7. a-Aminoisobutyric (Aib) residue is highly conformationally
restricted, with allowed conformations lying largely in the
region fꢀ 60ꢁ, cꢀ30ꢁ, see: (a) Toniolo, C.; Crisma, M.;
Formaggio, F.; Peggion, C. Biopolymers 2001, 60, 396–419;
(b) Kaul, R.; Balaram, P. Bioorg. Med. Chem. 1999, 7, 105–
117.
Acknowledgements
D.S. is thankful to CSIR, New Delhi for a research fellow-
ship.
8. Oligomers of aromatic amino acids and glycine that form self-
assembled duplex with high association constant have been
reported by Gong et al, see: (a) Zhu, J.; Parra, R. D.; Zeng,
H.; Jankun, E. S.; Zeng, X. C.; Gong, B. J. Am. Chem. Soc.
2000, 122, 4219–4220; (b) Gong, B. Chem.—Eur. J. 2001, 7,
4336–4342.
Supplementary data
Supplementary data associated with this article can be found
in the online version, at doi:10.1016/j.tet.2006.08.032.

10146
D. Srinivas et al. / Tetrahedron 62 (2006) 10141–10146
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14. For an excellent account on the graph set analysis of H-bonded
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15. This figure was generated using PyMOL molecular graphics
system. W. L. DeLano, The PyMOL Molecular Graphics
System. http://www.pymol.org (accessed 2004).
16. We have recently disclosed the compact, three-dimensional
structural architecture of acrylamide oligomers forming
protein b-sheet-like architecture, see: Amol, K.; Rajesh, R.;
Rajamohanan, P. R.; Sanjayan, G. J. Chem. Commun. 2006,
2756–2758.
12. Aib homo-oligomers assume a regular (right- and left-handed)
310-helical structure (a series of type III/III0 b-bends), see: Ref. 7.