4
1 Melanin Chemistry
Recently developed molecularly targeted drugs (e.g. targeted to V600E/K missense
mutation in the tyrosine kinase BRAF for inhibition of the cancer proliferation,
and to the negative regulatory immune receptor PD-1 for recovery of the cytotoxic
immunity) showed improved response rates [10, 11]. However, there are still unsolved
puzzles like the acquired resistance [12] as well as the adverse effects. The incident
rate of melanoma has shown an increasing tendency in recent years, indicating in part
a relation with increased UV exposure due to ozone layer depletion [13]. Therefore,
developing more effective anti-melanoma agents is an urgent issue.
Melanin is also attracting attention from condensed matter physics and material
sciences, as well as chemistry, biology, and medical sciences. The protective light
barrier function of melanin is due to the highly efficient energy conversion from the
absorbed light to heat [14]. Such energy-converting properties of melanin have been
investigated with a focus on their dynamics [15]. As well as the energy dissipation to
heat, photoconductive properties, which convert light energy to electric current, was
also observed [16]. From investigations on electric conduction through melanin, bistable conduction characteristics, which drastically switch its resistances at a certain
threshold voltage, were observed [17–20]. As such, properties of melanin might be
useful for electrical applications; several fabrication methods of melanin materials
were reported especially in a thin film form [16]. Biocompatible and biodegradable
nervous tissue responses of a fabricated melanin thin film were also confirmed, both
in vitro and in vivo [21]. This indicates the feasibility of melanin films for scaffold
applications in regeneration of nervous and muscular tissues. Furthermore, a coating
method by synthetic melanin using dopamine (dopamine-melanin) was reported as
a versatile surface-functionalization technique, which makes various combinations
of organic and/or inorganic (and metallic) surfaces adhesive to each other, indicating
feasibility of melanin also in applications to surface/interface sciences [22].
In summary, melanin study covers wide science fields, including materials science,
chemistry, and biology: synthetic melanin materials (e.g. thin films and adhesives),
the melanin biosynthesis system, and the reaction environment for the biosynthesis,
namely melanocyte. The reason for this broad attention to the melanin synthesizing
system might come from the connection to the visually simple phenotype “color”,
the oxidatively active reaction environment, and the wide variety of responses to
chemical and physical stimuli like the presence of ROS and light irradiation. Thus,
various research topics could emerge from exploration of this specialized environment for melanin biosynthesis. Accordingly, it is a fundamental problem to ask
mechanisms by which melanin biosynthesis proceeds and factors that can regulate
melanin biosynthesis.
The enzymes controlling melanin biosynthesis has been identified together with
their enzyme reactions. In spite of these existing enzymes, as described in the later
chapters, most of the processes involved in melanin biosynthesis spontaneously take
place without participation of enzymes. The presence of such spontaneous reactions
emphasizes a nature of non-enzymatic control of melanogenesis. As such control
of reactions does not exhibit very specific binding nature unlike typical enzymatic
processes, understanding melanin biosynthesis requires approaching unexplored
frontiers.
1 Melanin Chemistry
Recently developed molecularly targeted drugs (e.g. targeted to V600E/K missense
mutation in the tyrosine kinase BRAF for inhibition of the cancer proliferation,
and to the negative regulatory immune receptor PD-1 for recovery of the cytotoxic
immunity) showed improved response rates [10, 11]. However, there are still unsolved
puzzles like the acquired resistance [12] as well as the adverse effects. The incident
rate of melanoma has shown an increasing tendency in recent years, indicating in part
a relation with increased UV exposure due to ozone layer depletion [13]. Therefore,
developing more effective anti-melanoma agents is an urgent issue.
Melanin is also attracting attention from condensed matter physics and material
sciences, as well as chemistry, biology, and medical sciences. The protective light
barrier function of melanin is due to the highly efficient energy conversion from the
absorbed light to heat [14]. Such energy-converting properties of melanin have been
investigated with a focus on their dynamics [15]. As well as the energy dissipation to
heat, photoconductive properties, which convert light energy to electric current, was
also observed [16]. From investigations on electric conduction through melanin, bistable conduction characteristics, which drastically switch its resistances at a certain
threshold voltage, were observed [17–20]. As such, properties of melanin might be
useful for electrical applications; several fabrication methods of melanin materials
were reported especially in a thin film form [16]. Biocompatible and biodegradable
nervous tissue responses of a fabricated melanin thin film were also confirmed, both
in vitro and in vivo [21]. This indicates the feasibility of melanin films for scaffold
applications in regeneration of nervous and muscular tissues. Furthermore, a coating
method by synthetic melanin using dopamine (dopamine-melanin) was reported as
a versatile surface-functionalization technique, which makes various combinations
of organic and/or inorganic (and metallic) surfaces adhesive to each other, indicating
feasibility of melanin also in applications to surface/interface sciences [22].
In summary, melanin study covers wide science fields, including materials science,
chemistry, and biology: synthetic melanin materials (e.g. thin films and adhesives),
the melanin biosynthesis system, and the reaction environment for the biosynthesis,
namely melanocyte. The reason for this broad attention to the melanin synthesizing
system might come from the connection to the visually simple phenotype “color”,
the oxidatively active reaction environment, and the wide variety of responses to
chemical and physical stimuli like the presence of ROS and light irradiation. Thus,
various research topics could emerge from exploration of this specialized environment for melanin biosynthesis. Accordingly, it is a fundamental problem to ask
mechanisms by which melanin biosynthesis proceeds and factors that can regulate
melanin biosynthesis.
The enzymes controlling melanin biosynthesis has been identified together with
their enzyme reactions. In spite of these existing enzymes, as described in the later
chapters, most of the processes involved in melanin biosynthesis spontaneously take
place without participation of enzymes. The presence of such spontaneous reactions
emphasizes a nature of non-enzymatic control of melanogenesis. As such control
of reactions does not exhibit very specific binding nature unlike typical enzymatic
processes, understanding melanin biosynthesis requires approaching unexplored
frontiers.