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Novel pentapeptide activators of mammalian and mushroom tyrosinase.
[erythropoietic protoporphyria]
Melanoma
incidence
continues
to
rise
due
to
intentional
exposure
to
ultraviolet
radiation
(
UVR
)
from
sunlight
and
indoor
tanning
beds
.
Eumelanin
exhibits
photoprotective
effects
;
thus
,
agents
that
induce
its
synthesis
offer
a
means
for
sunless
tanning
without
UVR
damage
.
Herein
,
we
report
the
development
of
two
pentapeptides
,
P
9
and
P
10
,
capable
of
enhancing
melanin
synthesis
in
B
16
melanoma
cells
by
activating
mushroom
and
mouse
tyrosinases
without
any
effect
on
cell
viability
or
proliferation
.
P
9
and
P
10
significantly
increased
melanin
content
in
a
dose-dependent
manner
comparable
to
the
positive
controls
,
IBMX
,
scoparone
,
and
α-
MSH
.
However
,
unlike
IBMX
and
scoparone
,
but
similar
to
α-
MSH
,
P
9
and
P
10
were
able
to
reverse
6
BH
4
-
dependent
tyrosinase
inhibition
.
We
hypothesize
that
P
9
and
P
10
allosterically
activate
tyrosinase
and
consequently
enhance
epidermal
melanin
synthesis
.
P
9
and
P
10
may
offer
an
alternative
to
tanning
bed
use
and
non-photoprotective
tanning
products
.
Moreover
,
sustained
increase
of
melanin
content
in
skin
has
the
potential
to
reduce
symptoms
of
photosensitivity
disorders
such
as
erythropoietic
protoporphyria
(
EPP
)
,
solar
urticaria
(
SU
)
and
polymorphic
light
eruption
(
PLE
)
,
which
lack
fully
effective
treatments
and
result
in
significant
morbidity
.
Diseases
Validation
Diseases presenting
"positive controls"
symptom
cowden syndrome
erythropoietic protoporphyria
familial hypocalciuric hypercalcemia
krabbe disease
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