A large variety of peptoid side chains have been introduced (Fig. 3)
[24–27]. Moreover, commercially available automated peptide synthesizers can
be used for SPSS. Typically, SPSS is used to prepare sequence-specific peptoids,
but Rosales et al. have also demonstrated the successful preparation of highly
repetitive sequences that resemble homopolymers, without chain length dispersity
[28]. The SPSS is also ideally suited for automation to create large combinatorial
libraries via the mix-and-split method [15].
2.2 Living Polymerization of N-Substituted
N-Carboxyanhydrides
The preparation of peptoids by ring-opening polymerization (ROP) of
N-substituted N-carboxyanhydrides (NNCA, Fig. 1b–d) was first reported as early
as 1926 [29]. A few years earlier, the debate over whether macromolecules even
existed was still in progress [30], but by this time, Staudinger’s concept of polymers
[31] was well accepted. Also Sigmund and Wessely recognized the possible
formation of polymers in this first report on polysarcosine, without giving
any characterization of the substance. That came more than 20 years later, when
Waley and Watson studied the kinetics of the polymerization of sarcosine
N-carboxyanhydride (Sar-NCA) in the laboratories of Courtaulds Ltd. [32]. In
this contribution, Waley and Watson provide evidence that the Sar-NCA polymerization was one of the first polymerizations that – in retrospect – was found to
exhibit a living character, several years before Szwarc published his famous paper
entitled “‘Living’ polymers” [33].
We find it particularly remarkable that the living anionic and cationic polymerization of unsaturated compounds was a huge success, despite the relatively difficult
preparative conditions, while the living character of the Sar-NCA polymerization,
which is much easier to handle, went virtually unnoticed by the community (or at
least this is our perception 50 years later). Only a handful of research groups studied
this class of monomers during the following decades, and mainly to better understand polypeptides [34, 35]. Even less studied was polysarcosine as a material
[36–40].
Only a few years ago, Zhang and coworkers discovered a new way to polymerize
NNCAs, via catalysis using N-heterocyclic carbenes (Fig. 1d) [41]. In passing, they
reported on the living polymerization of N-butylglycine N-carboxyanhydride. This
was probably as remarkable as the main finding of the paper because, at that time,
only Sar-NCA had been studied in considerable detail. Since then, a few groups
have expanded the molecular toolkit of the NNCA polymerization considerably
(Fig. 4), but it certainly trails the versatility achievable with SPSS and is not likely
to get close in the foreseeable future [14, 42]. Side chain versatility of polymerized
peptoids is based on polymer analog modifications [43, 44]. However, polymerization of NNCAs gives access to linear [45, 46] or cyclic [47] hydrophilic,
Peptoids for Biomimetic Hierarchical Structures
395
[24–27]. Moreover, commercially available automated peptide synthesizers can
be used for SPSS. Typically, SPSS is used to prepare sequence-specific peptoids,
but Rosales et al. have also demonstrated the successful preparation of highly
repetitive sequences that resemble homopolymers, without chain length dispersity
[28]. The SPSS is also ideally suited for automation to create large combinatorial
libraries via the mix-and-split method [15].
2.2 Living Polymerization of N-Substituted
N-Carboxyanhydrides
The preparation of peptoids by ring-opening polymerization (ROP) of
N-substituted N-carboxyanhydrides (NNCA, Fig. 1b–d) was first reported as early
as 1926 [29]. A few years earlier, the debate over whether macromolecules even
existed was still in progress [30], but by this time, Staudinger’s concept of polymers
[31] was well accepted. Also Sigmund and Wessely recognized the possible
formation of polymers in this first report on polysarcosine, without giving
any characterization of the substance. That came more than 20 years later, when
Waley and Watson studied the kinetics of the polymerization of sarcosine
N-carboxyanhydride (Sar-NCA) in the laboratories of Courtaulds Ltd. [32]. In
this contribution, Waley and Watson provide evidence that the Sar-NCA polymerization was one of the first polymerizations that – in retrospect – was found to
exhibit a living character, several years before Szwarc published his famous paper
entitled “‘Living’ polymers” [33].
We find it particularly remarkable that the living anionic and cationic polymerization of unsaturated compounds was a huge success, despite the relatively difficult
preparative conditions, while the living character of the Sar-NCA polymerization,
which is much easier to handle, went virtually unnoticed by the community (or at
least this is our perception 50 years later). Only a handful of research groups studied
this class of monomers during the following decades, and mainly to better understand polypeptides [34, 35]. Even less studied was polysarcosine as a material
[36–40].
Only a few years ago, Zhang and coworkers discovered a new way to polymerize
NNCAs, via catalysis using N-heterocyclic carbenes (Fig. 1d) [41]. In passing, they
reported on the living polymerization of N-butylglycine N-carboxyanhydride. This
was probably as remarkable as the main finding of the paper because, at that time,
only Sar-NCA had been studied in considerable detail. Since then, a few groups
have expanded the molecular toolkit of the NNCA polymerization considerably
(Fig. 4), but it certainly trails the versatility achievable with SPSS and is not likely
to get close in the foreseeable future [14, 42]. Side chain versatility of polymerized
peptoids is based on polymer analog modifications [43, 44]. However, polymerization of NNCAs gives access to linear [45, 46] or cyclic [47] hydrophilic,
Peptoids for Biomimetic Hierarchical Structures
395