11.3 Functional Peptides 225mimetic if it also interacts with several other proteins or receptors that are
known to bind the natural ligand [101]. Mimicry is thus defined as “binding to
the same proteins as the natural ligand” rather than resembling the physico-
chemical properties or the molecular recognition characteristics of the ligand.
As mimicry is rarely obvious upon comparing the chemical structures of ligand
and mimotope, rational design of a peptide small molecule mimic is currently
nearly impossible.
Especially CMPs are of pharmaceutical relevance. Carbohydrates are often
displayed on the outer surfaces of pathogens and tumor cells and are therefore
potential immunological targets for diagnosis, antibody production, and vac-
cine development. However, carbohydrates are intrinsically T‐cell‐independent
antigens, which diminish their efficacy as immunogens [102]. Further, carbohy-
drates are difficult to chemically synthesize in high yield particularly due to the
absolute requirement for the correct stereoconfiguration [103]. In contrast,
preparative production routes to peptides have emerged over the last years
[104], and peptides have an absolute requirement for T cells, making them
better immunogens. The conversion of carbohydrate epitopes to peptide mimo-
topes has therefore potential to overcome the shortcomings of carbohydrate
immunogens [6].
The first attempt to establish a CMP using phage display was done with the
jack bean lectin concanavalin A (ConA), which binds α‐mannose. This effort led
to the identification of the tripeptide YPY to which ConA binds with high affinity
[105]. These studies were followed by the screening and successful identification
of a variety of peptide mimics against various pathogen‐ and virus‐associated
mono‐ and polysaccharides of high complexity. For a detailed and comprehen-
sive overview on available mimotopes and their applications, see [101].
The available studies support the remarkably high potential of peptides to
mimic virtually any desired chemical monomer or polymer – the right peptide
sequence simply needs to be discovered by an appropriate method such as phage
display. Although CMPs are traditionally chemically synthesized and – to the
best knowledge of this author – have not been inserted into a permissive site of a
protein scaffold, they illustrate the great versatility of potential chemical charac-
teristics and functions that peptides can adopt and that can even be expanded by
directed evolution. Consequently, as exemplified for peptide epitopes, the inser-
tion of mimotopes into protein scaffolds for structural stabilization or to simply
use theses scaffolds as carrier for in vivo delivery or high‐yield production might
bear a great but unexplored potential.
11.3.5.3 Antimicrobial Peptides
Antimicrobial peptides are short, mostly cationic hydrophobic peptides with
antimicrobial activity against a broad variety of microbes [106]. Although even
di‐ and tripeptides with antimicrobial activity have been reported [107], their
size usually varies from 7 [108] to about 60 aa residues [109]. Antimicrobial pep-
tides adopt secondary structures including α‐helices, relaxed coils, antiparallel
β‐sheets, and gamma‐core motifs – two antiparallel ββ‐sheets connected by a
short turn as found in defensin‐like peptides and often including disulfide
bridges. There is a relationship between structure and function, with amphipathic