Peptide Nanotubes: A Crystallographic Approach
99
planar residue as a whole. The shorter C
α and C
β bond (~1.33 Å, an ideal C=C double bond), increased planarity and the conjugation effects produce certain unfavorable steric interactions within the residue. This includes specifically, the steric clash
between CD1–H and N–H groups, which results in opening up of the bond angles
C
α =C
β –C
γ and N–C
α =C
β . These bond angles usually assume values of approximately 130° and 125°, respectively, in Phe containing peptides, indeed deviating
significantly from ideal trigonal value of 120° (Jain and Chauhan 1996; Mathur et al.
2004; Singh and Kaur 1996). Steric clash is released, in part by rotation around N–C
α
bond (ϕ) by approximately ±60° and in part by a slight deviation of the planarity of
the residue (non-zero values of χ
1 torsion angle). Besides, there is additional compensation for steric hindrance paid by the slight deviation in bond angles of N–C
α –C
and C
β =C
α –C
. There are shortening of N–C
α , C
α –C
, and C
β –C
γ single bond lengths
and elongation of C
=O double bond maybe due to partial conjugation of the C
α =C
β
bond and the peptide bond (Jain and Chauhan 1996; Mathur et al. 2004; Singh and
Kaur 1996). Thus the double bond between C
α and C
β introduces strong steric effects
in a dehydro residue resulting in a significant geometrical alteration.
2.1.3 Conformational Features of Phe
As mentioned earlier, the steric clash in Phe residue is released in part by the rotation
of ϕ ≈ +60° or −60°. When ϕ ≈ +60°, the allowed values of ψ can approximately
be +30° or +150° after removing the steric clashes. Similarly when ϕ ≈ −60°,
ψ can be approximately −30° or −150°. Thus from the simple model building
studies it has been inferred that the most favourable conformation for Phe residues
is (ϕ, ψ) ≈ (60°, 30°), (60°, −30°), (60°, 150°), (−60°, −150°). The theoretical
conformational studies have suggested that there are six energy minima possible for
Phe residue (Ajo et al. 1982). However, experimentally observed conformations
are approximately close to a few of these minima. To date, approximately 50 crystal
structures of peptides containing Phe residues have been reported. The analyses
of these structures suggest that Phe residue can assume conformations (ϕ, ψ) ~
(−60°, −30°), (−60°, 150°), (−80°, 0) or their enantiomers (Mathur et al. 2004;
Singh et al. 1990; Singh and Kaur 1996). Figure 5 shows the Ramachandran map
for Phe containing peptides, in which the observed (ϕ, ψ) values are plotted.
It is clear that a majority of the observed (ϕ, ψ) values are in helical regions in
the Ramachandran map. As a consequence, the experimental results from X-ray
crystallography match with the model building observations and partially with the
theoretical conformational analyses, though the helical region is highly preferred.
This work highlights the inclusion of a non-coded, achiral, conformation
constraining α, β-dehydrophenylalanine (Phe) residue in the dipeptide, to
probe the process of molecular self-assembly. Incorporation of dehydroamino
acids provides the peptide with unique properties: rigidity, increased hydrophobicity, electrophilic reactivity, the restricted orientation of β-substituents and resistance
to enzymatic degradation. The conformational flexibility of both, the dehydro peptide
backbone as well as the specific side chain of the dehydro residue, is expected to be
99
planar residue as a whole. The shorter C
α and C
β bond (~1.33 Å, an ideal C=C double bond), increased planarity and the conjugation effects produce certain unfavorable steric interactions within the residue. This includes specifically, the steric clash
between CD1–H and N–H groups, which results in opening up of the bond angles
C
α =C
β –C
γ and N–C
α =C
β . These bond angles usually assume values of approximately 130° and 125°, respectively, in Phe containing peptides, indeed deviating
significantly from ideal trigonal value of 120° (Jain and Chauhan 1996; Mathur et al.
2004; Singh and Kaur 1996). Steric clash is released, in part by rotation around N–C
α
bond (ϕ) by approximately ±60° and in part by a slight deviation of the planarity of
the residue (non-zero values of χ
1 torsion angle). Besides, there is additional compensation for steric hindrance paid by the slight deviation in bond angles of N–C
α –C
and C
β =C
α –C
. There are shortening of N–C
α , C
α –C
, and C
β –C
γ single bond lengths
and elongation of C
=O double bond maybe due to partial conjugation of the C
α =C
β
bond and the peptide bond (Jain and Chauhan 1996; Mathur et al. 2004; Singh and
Kaur 1996). Thus the double bond between C
α and C
β introduces strong steric effects
in a dehydro residue resulting in a significant geometrical alteration.
2.1.3 Conformational Features of Phe
As mentioned earlier, the steric clash in Phe residue is released in part by the rotation
of ϕ ≈ +60° or −60°. When ϕ ≈ +60°, the allowed values of ψ can approximately
be +30° or +150° after removing the steric clashes. Similarly when ϕ ≈ −60°,
ψ can be approximately −30° or −150°. Thus from the simple model building
studies it has been inferred that the most favourable conformation for Phe residues
is (ϕ, ψ) ≈ (60°, 30°), (60°, −30°), (60°, 150°), (−60°, −150°). The theoretical
conformational studies have suggested that there are six energy minima possible for
Phe residue (Ajo et al. 1982). However, experimentally observed conformations
are approximately close to a few of these minima. To date, approximately 50 crystal
structures of peptides containing Phe residues have been reported. The analyses
of these structures suggest that Phe residue can assume conformations (ϕ, ψ) ~
(−60°, −30°), (−60°, 150°), (−80°, 0) or their enantiomers (Mathur et al. 2004;
Singh et al. 1990; Singh and Kaur 1996). Figure 5 shows the Ramachandran map
for Phe containing peptides, in which the observed (ϕ, ψ) values are plotted.
It is clear that a majority of the observed (ϕ, ψ) values are in helical regions in
the Ramachandran map. As a consequence, the experimental results from X-ray
crystallography match with the model building observations and partially with the
theoretical conformational analyses, though the helical region is highly preferred.
This work highlights the inclusion of a non-coded, achiral, conformation
constraining α, β-dehydrophenylalanine (Phe) residue in the dipeptide, to
probe the process of molecular self-assembly. Incorporation of dehydroamino
acids provides the peptide with unique properties: rigidity, increased hydrophobicity, electrophilic reactivity, the restricted orientation of β-substituents and resistance
to enzymatic degradation. The conformational flexibility of both, the dehydro peptide
backbone as well as the specific side chain of the dehydro residue, is expected to be