Z-Lys
ε-Carbobenzyloxy-L-lysine
α-gal-C
α,D-Galactopyranosyl-L-cysteine
α-gal-C
O2
α,D-Galactopyranosyl-L-cysteine sulfone
1 Introduction
Biological systems produce proteins that possess the ability to self-assemble into
complex, yet highly ordered structures [1]. These remarkable materials are polypeptide copolymers that derive their properties from precisely controlled sequences and
compositions of their constituent amino acid monomers. There has been recent
interest in developing synthetic routes for preparation of these natural polymers as
well as de novo designed polypeptide sequences to make products for applications in
medicine (artificial tissue, implants), biomineralization (resilient, lightweight,
ordered inorganic composites), and analysis (biosensors, medical diagnostics) [2, 3].
To be successful in these applications, it is important that materials can selfassemble into precisely defined structures. Polypeptides have many advantages over
conventional synthetic polymers because they are able to adopt stable ordered
conformations [4]. Depending on the amino acid side chain substituents, polypeptides
are able to adopt a multitude of conformationally stable regular secondary structures
(helices, sheets, turns), tertiary structures (e.g., the β-strand–helix–β-strand unit
found in β-barrels), and quaternary assemblies (e.g., collagen microfibrils) [4]. The
synthesis of polypeptides that can assemble into non-natural structures is an attractive
challenge for polymer chemists.
Synthetic peptide-based polymers are not new materials: homopolymers of
polypeptides have been available for many decades; yet, partially due to their
heterogeneous nature, they have only seen limited use as structural materials
[5, 6]. In recent decades, improved methods in chemical synthesis have made
possible the preparation of increasingly complex copolypeptide sequences of
controlled molecular weight that display properties far superior to ill-defined
homopolypeptides [7]. Furthermore, block copolypeptides, which combine different
structural and functional peptide elements, have been prepared and begin to mimic
some of the complexities of proteins [8]. These polymers are well suited for
applications where polymer assembly and functional domains need to be at length
scales ranging from nanometers to microns. These block copolypeptides are
macroscopically homogeneous as solids, but dissimilarity between the block
segments typically results in phase separation in aqueous media [9]. Synthesis of
simple hydrophilic/hydrophobic diblock copolypeptides, when dispersed in water,
allows formation of peptide-based micelles, vesicles, and hydrogels that are
potentially useful in biomedical applications [10]. The regular secondary structures
Synthesis and Self-Assembly of Well-Defined Block Copolypeptides via. . .
3
ε-Carbobenzyloxy-L-lysine
α-gal-C
α,D-Galactopyranosyl-L-cysteine
α-gal-C
O2
α,D-Galactopyranosyl-L-cysteine sulfone
1 Introduction
Biological systems produce proteins that possess the ability to self-assemble into
complex, yet highly ordered structures [1]. These remarkable materials are polypeptide copolymers that derive their properties from precisely controlled sequences and
compositions of their constituent amino acid monomers. There has been recent
interest in developing synthetic routes for preparation of these natural polymers as
well as de novo designed polypeptide sequences to make products for applications in
medicine (artificial tissue, implants), biomineralization (resilient, lightweight,
ordered inorganic composites), and analysis (biosensors, medical diagnostics) [2, 3].
To be successful in these applications, it is important that materials can selfassemble into precisely defined structures. Polypeptides have many advantages over
conventional synthetic polymers because they are able to adopt stable ordered
conformations [4]. Depending on the amino acid side chain substituents, polypeptides
are able to adopt a multitude of conformationally stable regular secondary structures
(helices, sheets, turns), tertiary structures (e.g., the β-strand–helix–β-strand unit
found in β-barrels), and quaternary assemblies (e.g., collagen microfibrils) [4]. The
synthesis of polypeptides that can assemble into non-natural structures is an attractive
challenge for polymer chemists.
Synthetic peptide-based polymers are not new materials: homopolymers of
polypeptides have been available for many decades; yet, partially due to their
heterogeneous nature, they have only seen limited use as structural materials
[5, 6]. In recent decades, improved methods in chemical synthesis have made
possible the preparation of increasingly complex copolypeptide sequences of
controlled molecular weight that display properties far superior to ill-defined
homopolypeptides [7]. Furthermore, block copolypeptides, which combine different
structural and functional peptide elements, have been prepared and begin to mimic
some of the complexities of proteins [8]. These polymers are well suited for
applications where polymer assembly and functional domains need to be at length
scales ranging from nanometers to microns. These block copolypeptides are
macroscopically homogeneous as solids, but dissimilarity between the block
segments typically results in phase separation in aqueous media [9]. Synthesis of
simple hydrophilic/hydrophobic diblock copolypeptides, when dispersed in water,
allows formation of peptide-based micelles, vesicles, and hydrogels that are
potentially useful in biomedical applications [10]. The regular secondary structures
Synthesis and Self-Assembly of Well-Defined Block Copolypeptides via. . .
3