ANALGESIC ACTIVITY OF A POLYPEPTIDE
MODULATOR OF TRPV1 RECEPTORS
I. A. D’yachenko,
G. I. Belous,
L. A. Skobtsova,
T. Yu. Zharmukhamedova,
V. A. Palikov,
Yu. A. Palikova,
E. V. D’yachenko,
E. A. Kalabina,
V. B. Rudenko,
Ya. A. Andreev,
Yu. A. Logashina,
S. A. Kozlov,
A. N. Yavorskii,
and A. N. Murashev
Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 52, No. 3, pp. 25 – 27, March, 2018.
Original article submitted December 23, 2016.
The activity of APHC2, a new polypeptide modulator of TRPV1 receptors that was isolated from Heteractis
crispa, is studied. It was established that APHC2 possessed analgesic properties, did not disturb normal loco
motor activity, and did not change body temperature and hemostasis of experimental animals. These attributes
could be of great practical value for designing a new generation of efficacious analgesics. A brief increase of
heart rate was observed during studies of the hemodynamic activity. Further investigation of the binding spe-
cifics of this polypeptide with TRPV1 receptors could open approaches to discovering other antagonists of
Keywords: polypeptide modulator, TRPV1 receptors, analgesics.
The TRPV1 receptor interacts with capsaicin and is the
most well-known and studied of the ionotropic TRP recep-
tors [1, 2]. The TRPV1 receptor plays a significant role in
many biological processes such as perception of the external
temperature (>43°C), development of inflammation, and
thermal regulation [1, 2]. Activation of TRPV1 induces pain,
reduces body temperature, increases sweating, and results in
increased sensitivity to painful stimuli (hyperalgesia) or
painful sensations in response to non-painful stimuli
(allodynia) [1, 2]. Thus, the TRPV1 receptor is an extremely
interesting target for new analgesics and anti-inflammatory
Previously, TRPV1 modulators were detected and char
acterized by us from the extract of the marine anemone
Heteractis crispa (APHC1 and APHC3). They exhibited pro
nounced analgesic activity and reduced the body temperature
of experimental animals [3-7]. A polypeptide component that
was called APHC2 was also found in this extract. However,
its biological activity was not studied in detail. APHC2 was a
weak inhibitor of serine protease and modulator of TRPV1
receptor activity .
The polypeptide APHC2 was produced by heterologous
expression in a hybrid protein with thioredoxin in E. coli
cells. The pure peptide was obtained by purifying the hybrid
protein using metal-affinity chromatography over a
-sorbent, cleaving with cyanogen bromide, and isolating
the target product using RP-HPLC, as reported earlier
[4, 5, 8]. The purity of the obtained peptide according to ana
lytical HPLC and mass spectrometry was >96%.
The present work focused on studies of the biological ac
tivity of this polypeptide in experimental models.
Pharmaceutical Chemistry Journal, Vol. 52, No. 3, June, 2018 (Russian Original Vol. 52, No. 3, March, 2018)
0091-150X/18/5203-0213 © 2018 Springer Science+Business Media, LLC
Pushchino Branch of the Shemyakin—Ovchinnikov Institute of Bioor
ganic Chemistry (BIBC), Russian Academy of Sciences, 6 Prosp. Nauki,
Pushchino, Moscow Oblast, 142290 Russia.
Pushchino Scientific Center, Russian Academy of Sciences, 3 Prosp.
Nauki, Pushchino, Moscow Oblast, 142290 Russia.
Pushchino State Institute of Natural Sciences, 3 Prosp. Nauki, Pushchino,
Moscow Oblast, 142290 Russia.
Shemyakin—Ovchinnikov Institute of Bioorganic Chemistry (IBC), Rus
sian Academy of Sciences, 16/10 Miklukho-Maklaya St., Moscow,
Institute of Molecular Medicine, I. M. Sechenov First Moscow State Med
ical University, 8 Trubetskaya St., Moscow, 119991 Russia.
Scientific Center for Expert Evaluation of Medicinal Products, Ministry of
Health of the Russian Federation, 8 Petrovskii Blvd., Moscow, 127051