with steric effects of residues) favors the formation of secondary structures, i.e. the
local spatial arrangement of the linear chain into turns, helices, sheets, and ribbons.
The 3D spatial arrangement of such secondary structures in relation to each other
eventually leads us to tertiary structures. If several, duly ordered peptide chains
assembly into a well-defined functional superstructure, we use the term quaternary
structure. Hemoglobin represents such an assembly, but the term quaternary structure is also used at times for much more complex structures such as virus capsids [4]
or chromatin [5].
Very recently, synthetic biologists have been working successfully to rival the
structural versatility found in proteins. Using the so-called DNA origami, very
intricate patterns were created, albeit often in 2D on surfaces [6]. Although the
natural versatility and complexity of RNAs should not go unmentioned, we will
concentrate here on peptidomimetic structures for reasons that should become
apparent.
The exact control over the hierarchical structure of proteins is of paramount
importance for their biological function. Minor errors can have devastating effects.
Alzheimer’s disease is only one of many severe medical disorders that can be traced
to misfolding of proteins [7].
Folding and misfolding of proteins is a complex event that in nature takes place
in the complex intracellular environment [8]. The secondary structure formation is
driven strongly by the nature of the primary structure, with some amino acids being
strong promoters of α-helices and others favoring the formation of β-sheets. Hydrogen bonding is an important factor in these processes and formation of these
secondary structures is much faster than the overall assembly (see [9] and
references therein). The formation of tertiary structures, however, requires more
time and appears to be guided not so much by the secondary structure but more by
the topology or contact order, which is the average distance of residues in the
primary sequence that are in contact in the folded state. In this case, hydrophobic
interactions are an important factor [10, 11].
Here, we review the possibilities for the formation of hierarchical structures
using peptoids. Peptoids comprise an oligo- or polyglycine backbone but are, in
contrast to peptides, substituted at the amide nitrogen. For the sake of readability,
we do not differentiate between oligopeptoids and polypeptoids in this account. It is
also noted that we do not differentiate per se between uniform and non-uniform
peptoids although we are aware that there are major differences. We would rather
differentiate on a case-by-case basis. In general, however, in the vast majority of
cases for which hierarchical peptoid structures have been reported, the peptoids
were uniform oligopeptoids.
We would like to draw the attention of the interested reader to several previous
review articles on polypeptoids, some of them similar in design and scope to our
present contribution [12–14]. In particular, we would like to refer to a beautiful
contribution by Zuckerman, in which he outlined the “Peptoid Origins” [15]. Similarly, the brief yet comprehensive commentary by Wetzler and Barron describes the
“progress in the de novo design of structured peptoid protein mimics” [16].
Peptoids for Biomimetic Hierarchical Structures
391
local spatial arrangement of the linear chain into turns, helices, sheets, and ribbons.
The 3D spatial arrangement of such secondary structures in relation to each other
eventually leads us to tertiary structures. If several, duly ordered peptide chains
assembly into a well-defined functional superstructure, we use the term quaternary
structure. Hemoglobin represents such an assembly, but the term quaternary structure is also used at times for much more complex structures such as virus capsids [4]
or chromatin [5].
Very recently, synthetic biologists have been working successfully to rival the
structural versatility found in proteins. Using the so-called DNA origami, very
intricate patterns were created, albeit often in 2D on surfaces [6]. Although the
natural versatility and complexity of RNAs should not go unmentioned, we will
concentrate here on peptidomimetic structures for reasons that should become
apparent.
The exact control over the hierarchical structure of proteins is of paramount
importance for their biological function. Minor errors can have devastating effects.
Alzheimer’s disease is only one of many severe medical disorders that can be traced
to misfolding of proteins [7].
Folding and misfolding of proteins is a complex event that in nature takes place
in the complex intracellular environment [8]. The secondary structure formation is
driven strongly by the nature of the primary structure, with some amino acids being
strong promoters of α-helices and others favoring the formation of β-sheets. Hydrogen bonding is an important factor in these processes and formation of these
secondary structures is much faster than the overall assembly (see [9] and
references therein). The formation of tertiary structures, however, requires more
time and appears to be guided not so much by the secondary structure but more by
the topology or contact order, which is the average distance of residues in the
primary sequence that are in contact in the folded state. In this case, hydrophobic
interactions are an important factor [10, 11].
Here, we review the possibilities for the formation of hierarchical structures
using peptoids. Peptoids comprise an oligo- or polyglycine backbone but are, in
contrast to peptides, substituted at the amide nitrogen. For the sake of readability,
we do not differentiate between oligopeptoids and polypeptoids in this account. It is
also noted that we do not differentiate per se between uniform and non-uniform
peptoids although we are aware that there are major differences. We would rather
differentiate on a case-by-case basis. In general, however, in the vast majority of
cases for which hierarchical peptoid structures have been reported, the peptoids
were uniform oligopeptoids.
We would like to draw the attention of the interested reader to several previous
review articles on polypeptoids, some of them similar in design and scope to our
present contribution [12–14]. In particular, we would like to refer to a beautiful
contribution by Zuckerman, in which he outlined the “Peptoid Origins” [15]. Similarly, the brief yet comprehensive commentary by Wetzler and Barron describes the
“progress in the de novo design of structured peptoid protein mimics” [16].
Peptoids for Biomimetic Hierarchical Structures
391