3.2 Self-Assembly and Dynamics of Polypeptides
It is remarkable that Hermann Staudinger had already considered synthetic and
biomacromolecules in parallel and noted their similarities as well as their differences
[1]. Following this, we note that local chain conformations also play a vital role in the
organization of polypeptides, i.e., macromolecules composed of amino acids. Resembling biomacromolecules, they are considered for use in drug delivery and gene
therapy and thus have been the subject of intensive studies [50, 51]. In addition, it is
known that the superb performance of biological polypeptide-based materials such as
hair or spiders’ silk is due to a hierarchical superstructure over several length scales,
where structure control is exerted at every level of hierarchy [52]. The two most
common local conformations of polypeptides, known as secondary structures, are the
α-helix, stabilized by intramolecular hydrogen bonds, and the β-sheet, stabilized by
intermolecular hydrogen bonds. These secondary structures can be probed directly by
solid state NMR [14] and their packing can be obtained from X-ray studies
[53]. In addition, the α-helical structure posts a permanent dipole moment along its
backbone and can, therefore, be classified as a type-A polymer in Stockmayer’s
classification [54]. This dipole moment can be measured precisely using dielectric
spectroscopy (DS) and can be used as a probe of the persistence length of the
secondary structure [55]. Over the years, we have studied various polypeptides by
different NMR techniques, X-ray scattering, and dielectric spectroscopy [8] in order
to better understand their hierarchical self-assembly (Fig. 3).
As shown in an extended review [56], the concerted application of these techniques has shed light into the origin of the glass transition, the persistence of the
α-helical peptide secondary motif, and the effects of topology and packing on the type
and persistence of secondary structures. Protein function and application often depend
on these issues. Using poly(γ-benzyl-L-glutamate), PBLG, as an example, it was
shown that helices are objects of rather low persistence in the bulk as well as in
concentrated solutions in helicogenic solvents.
Copolypeptides, on the other hand, with their inherent nanometer length scale of
phase separation, provide means of manipulating both the type and persistence
of peptide secondary structures. As examples, we refer to the partial annihilation of
α-helical structural defects due to chain stretching, to the induced chain folding of
β-sheets in block copolypeptides with incommensurate dimensions, and to the destabilization of β-sheets in peptidic blocks having both secondary motifs [57, 58]. These
effects should be taken into account when such peptides are going to be employed. in
applications such as drug delivery.
Proline residues are of exceptional significance in protein conformation and
protein folding because proline is the only amino acid where the nitrogen bears no
amide hydrogen, preventing hydrogen bonding. Furthermore, the bulky pyrrolidine
ring restricts the available conformations. Therefore, polypeptides with proline residues offer a unique possibility for unraveling the interplay between hydrogen
bonding and geometric packing effects. In a recent multi-technique study of diblock
copolymers of PBLG and poly(L-proline) (PLP) their hierarchical self-assembly was
302
H.W. Spiess
It is remarkable that Hermann Staudinger had already considered synthetic and
biomacromolecules in parallel and noted their similarities as well as their differences
[1]. Following this, we note that local chain conformations also play a vital role in the
organization of polypeptides, i.e., macromolecules composed of amino acids. Resembling biomacromolecules, they are considered for use in drug delivery and gene
therapy and thus have been the subject of intensive studies [50, 51]. In addition, it is
known that the superb performance of biological polypeptide-based materials such as
hair or spiders’ silk is due to a hierarchical superstructure over several length scales,
where structure control is exerted at every level of hierarchy [52]. The two most
common local conformations of polypeptides, known as secondary structures, are the
α-helix, stabilized by intramolecular hydrogen bonds, and the β-sheet, stabilized by
intermolecular hydrogen bonds. These secondary structures can be probed directly by
solid state NMR [14] and their packing can be obtained from X-ray studies
[53]. In addition, the α-helical structure posts a permanent dipole moment along its
backbone and can, therefore, be classified as a type-A polymer in Stockmayer’s
classification [54]. This dipole moment can be measured precisely using dielectric
spectroscopy (DS) and can be used as a probe of the persistence length of the
secondary structure [55]. Over the years, we have studied various polypeptides by
different NMR techniques, X-ray scattering, and dielectric spectroscopy [8] in order
to better understand their hierarchical self-assembly (Fig. 3).
As shown in an extended review [56], the concerted application of these techniques has shed light into the origin of the glass transition, the persistence of the
α-helical peptide secondary motif, and the effects of topology and packing on the type
and persistence of secondary structures. Protein function and application often depend
on these issues. Using poly(γ-benzyl-L-glutamate), PBLG, as an example, it was
shown that helices are objects of rather low persistence in the bulk as well as in
concentrated solutions in helicogenic solvents.
Copolypeptides, on the other hand, with their inherent nanometer length scale of
phase separation, provide means of manipulating both the type and persistence
of peptide secondary structures. As examples, we refer to the partial annihilation of
α-helical structural defects due to chain stretching, to the induced chain folding of
β-sheets in block copolypeptides with incommensurate dimensions, and to the destabilization of β-sheets in peptidic blocks having both secondary motifs [57, 58]. These
effects should be taken into account when such peptides are going to be employed. in
applications such as drug delivery.
Proline residues are of exceptional significance in protein conformation and
protein folding because proline is the only amino acid where the nitrogen bears no
amide hydrogen, preventing hydrogen bonding. Furthermore, the bulky pyrrolidine
ring restricts the available conformations. Therefore, polypeptides with proline residues offer a unique possibility for unraveling the interplay between hydrogen
bonding and geometric packing effects. In a recent multi-technique study of diblock
copolymers of PBLG and poly(L-proline) (PLP) their hierarchical self-assembly was
302
H.W. Spiess