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Journal Name
peptide P3 with 4,4-dimethyl substituted
COMMUNICATION
-amino acid (Aic) β-peptides. The Aib and other achiral dialkyl-substituted α-
DOI: 10.1039/C9C-pCe0p74ti1d3Ae
displayed weak NH(1)
CβH(1) NH(2) and CβH(3)
CH
NH(2) as well as medium amino acids have been widely used to control the
NH(4) NOEs and strong sequential conformation by limiting the accessible conformational space
NH in the ROESY spectrum. Similar to P1 and P2 small through Thorpe–Ingold effect.18 This conformational restriction
change in the chemical shifts of amide NHs observed during the of Aib residues promote helical conformation in α-peptides. In
DMSO titration except C-terminal amide proton (Aic4 NH) is continuation, incorporation of Aib residue as a guest into the β-
suggesting its participation in intramolecular H-bonding. Using peptide 14-helix leads to transformation of 14-helix into 12-
NOE and H-bonding restraints, the solution structures of P1,
P2, helix.19 It is interesting to note that insertion of homologated
and P3 were generated and the superposition of 10 lowest analogue of Aib, β3HAib, into a β-peptides prevent formation of
energy minimized structure are shown in Figure 1. Strikingly, all 14-helix confroamtions.20 Our report indicates that achiral 3,3-
three β,
-hybrid peptides adopted 11-helical
(
-helix) dialkyl substituted as well as 4,4-dialkyl
-amino acid in the
conformation in solution.
hybrid sequence could be used to access the otherwise
Further, we examined the conformations of the peptides P2 and inaccessible conformational space.
P3 in CD3OH to understand the stability of 11-helix in polar In conclusion, we have demonstrated the unique 11-helix
1
solvents. Both P2 and P3 showed well resolved H NMR in conformations of β,
-hybrid peptides composed with β-leucine
-amino acids in solution.
NH(4) and The helical structures are stabilized by the continuous 11-
NH(6) NOEs in P2 and weak NH(1)-NH(2), strong membered (i i+1) H-bonds in the reverse direction, which is in
NH(2) and CβH(3)
NH(4)NOEs in P3 similar to the sharp contrast with the -helix. Overall, the new helix type
-hybrid peptides reported here will open up new
CD3OH (5 mM). The ROESY experiments revealed weak NH(1)- and 3,3- and 4,4-dimethyl substituted
NH(2), and strong CβH(1)
NH(2), CβH(3)
CβH(5)
CβH(1)
NOEs observed in CDCl3, suggesting similar conformational from β,
behaviour of the peptides P2 and P3 in CD3OH. The possibilities to design new peptide foldamers.
superposition of 10 lowest energy minimized structures of the
peptide P2 using NOE and H-bonding restraints is shown in the R. M is thankful to CSIR-India for research fellowship. H. N. G.
Figure1D.
thanks SERB, DST, Govt. of India for financial support.
Along with NMR, we invoked the infrared absorption
spectroscopy to understand H-bonding of peptides in CDCl3. All References
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peptides displayed the NH stretching frequency (amide A) in the
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involvement of amide NHs in H-bonding with the exception of
C-terminal NH group. The absorption band of this free C-
terminal NH group is very weak. The concentration dependent
IR investigations (See ESI Figure S33) suggested negligible
change in NH stretching frequencies expect the change in
intensity, indicating their involvement in the intramolecular H-
bonds.17
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the native
Supporting Information. The hydrogen bond distances were
found to be in the range of 1.8 to 2.5 Å. The torsion angle
adopted gauche+ (g+) conformation along Cβ-C in β-residues
and and showed values with +++ sign. The backbone
conformation of -residues in 11-helix is quite different from
that of 13-helix in β -hybrid peptides as well as 12- or 15/17-
helix in -hybrid peptides. The
-residues displayed gauche+
(g+) and gauche- (g-) local conformations along Cβ–C and Cα–Cβ
bonds, respectively. The 1 2 and variable displayed the
-helix. The torsion angles are tabulated in the
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7868.
+, +, - and + respectively. In addition, the torsion angle
adopted regular trans geometry. The torsion values of -
residues are consistent with reported theoretical values. Our
findings reported here are nicely correlates with the Hofmann’s
predictions expect the torsion angle parameters of β-residues.8
More importantly, accommodation of stereochemically
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unfavorable g+, g- along the C-Cβ and Cβ-C in
interesting. The N to C terminal H-bonding direction observed
in the 11-helix of β, -hybrid peptides resembles the 14-helix in
-residues is quite
12. P. G. Vasudev, K. Ananda, S. Chatterjee, S. Aravinda, N. Shamala
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