Here, we aim to give our perspective on the advances, remaining problems, and
potential of biomimetic hierarchical structure that can be (potentially) created from
polypeptoids. In our opinion, of the different synthetic polymers, polypeptoids form
a very interesting platform for the study of complex hierarchical structure.
2 Primary Structure: Synthetic Possibilities
The primary structure of a polypeptide or any other polymer (i.e. the sequence of
monomer units) is defined by the synthesis of the polymer. Alternatively, modification after polymer synthesis may alter the identity of certain moieties. This is
called polymer analog(ue or ous) modification by polymer chemists, or posttranslational modification [17] in protein biosynthesis. In both cases, this may [18] or
may not [19] involve some changes in the sequence of the monomer units; more
often, this is not the case.
The dispersity of a macromolecule is a defining factor thereof. The method by
which a polymer is synthesized is directly related to its dispersity Ð (Ð ¼ M w /M n )
[20]. Non-controlled polymerizations such as free radical polymerization or stepgrowth polymerization should yield dispersities of Ð % 2, in theory. Controlled
radical polymerizations will often yield dispersities below 1.2, and many colleagues
refer to such products as monodisperse. So-called living polymerizations should
ideally lead to polymers that have a molar mass distribution that follows a Poisson
distribution (if initiation is considerably faster than propagation), for which the
dispersity should depend solely on the degree of polymerization (DP) (Ð % 1 + 1/
DP). This is the lowest dispersity that can be achieved via polymerization. To
obtain even better-defined polymers, we need to use iterative synthesis methods,
such as solid phase peptide synthesis (SPPS), which was pioneered by Merrifield.
Solid phase organic synthesis is, in general, a widely applicably concept that can be
used to create sequence-specific oligomers or small polymers such as oligo(mphenylene ethynylene)s [21]. More regularly, polymers containing amide bonds
between the repeat units are prepared [22]. The solid-phase submonomer synthesis
(SPSS) of peptoids is very similar to the Merrifield approach. However, some
modifications result in synthetic advantages, which will be discussed briefly below.
2.1 Iterative Synthesis
The solid phase-supported synthesis of peptoids was first reported using protected
and N-substituted amino acids [23]. A major bottleneck of this approach was the
difficult and expensive monomer synthesis. Accordingly, Zuckermann and
coworkers developed a different approach in which a monomer unit is formed in
two reaction steps. First, a haloacetic acid is coupled to the resin and, second, S N 2
substitution of the halogen with a primary amine takes place (Fig. 1a). The crucial
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N. Gangloff and R. Luxenhofer
potential of biomimetic hierarchical structure that can be (potentially) created from
polypeptoids. In our opinion, of the different synthetic polymers, polypeptoids form
a very interesting platform for the study of complex hierarchical structure.
2 Primary Structure: Synthetic Possibilities
The primary structure of a polypeptide or any other polymer (i.e. the sequence of
monomer units) is defined by the synthesis of the polymer. Alternatively, modification after polymer synthesis may alter the identity of certain moieties. This is
called polymer analog(ue or ous) modification by polymer chemists, or posttranslational modification [17] in protein biosynthesis. In both cases, this may [18] or
may not [19] involve some changes in the sequence of the monomer units; more
often, this is not the case.
The dispersity of a macromolecule is a defining factor thereof. The method by
which a polymer is synthesized is directly related to its dispersity Ð (Ð ¼ M w /M n )
[20]. Non-controlled polymerizations such as free radical polymerization or stepgrowth polymerization should yield dispersities of Ð % 2, in theory. Controlled
radical polymerizations will often yield dispersities below 1.2, and many colleagues
refer to such products as monodisperse. So-called living polymerizations should
ideally lead to polymers that have a molar mass distribution that follows a Poisson
distribution (if initiation is considerably faster than propagation), for which the
dispersity should depend solely on the degree of polymerization (DP) (Ð % 1 + 1/
DP). This is the lowest dispersity that can be achieved via polymerization. To
obtain even better-defined polymers, we need to use iterative synthesis methods,
such as solid phase peptide synthesis (SPPS), which was pioneered by Merrifield.
Solid phase organic synthesis is, in general, a widely applicably concept that can be
used to create sequence-specific oligomers or small polymers such as oligo(mphenylene ethynylene)s [21]. More regularly, polymers containing amide bonds
between the repeat units are prepared [22]. The solid-phase submonomer synthesis
(SPSS) of peptoids is very similar to the Merrifield approach. However, some
modifications result in synthetic advantages, which will be discussed briefly below.
2.1 Iterative Synthesis
The solid phase-supported synthesis of peptoids was first reported using protected
and N-substituted amino acids [23]. A major bottleneck of this approach was the
difficult and expensive monomer synthesis. Accordingly, Zuckermann and
coworkers developed a different approach in which a monomer unit is formed in
two reaction steps. First, a haloacetic acid is coupled to the resin and, second, S N 2
substitution of the halogen with a primary amine takes place (Fig. 1a). The crucial
392
N. Gangloff and R. Luxenhofer