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Protein & Peptide Letters, 2018, 25, 612-618

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Phosphodiesterases (PDEs) from Snake Venoms: Therapeutic Applications

BENTHAM Editor-in-Chief:
SCIENCE Ben M. Dunn

Bushra Uzair1, Barkat A. Khan2,*, Noureen Sharif1, Faiza Shabbir1 and Farid Menaa3

1
Department of Biotechnology and Bioinformatics, Islamic International University, Islamabad, Pakistan; 2Department
of Pharmaceutics, Faculty of Pharmacy, Gomal University, D.I Khan, Pakistan; 3Department of Pharmaceutical
Sciences and Nanomedicine, Fluorotronics, San Diego, CA, USA

ARTICLE HISTORY
Received: January 28, 2017
Revised: April 23, 2017
Accepted: March 12, 2018
DOI:
10.2174/0929866525666180628160616
Protein & Peptide Letters
Abstract: Background: Snake venom, a highly poisonous and active venomous snake’s secretion,
is a complex mixture of inorganic cations, carbohydrates, lipids, proteins, peptides, toxins and hy-
drolytic enzymes of importance including Phosphodiesterases (PDEs). These snake venom hydro-
lytic enzymes interfere in different physiological processes. Snake venom PDEs have several roles
to metabolize extracellular nucleotides and to regulate nucleotide based intercellular signalling
mechanisms including platelet aggregation, which can lead to death and debilitation in cardiac ar-
rest and strokes in patients having cerebro-vascular and cardiovascular diseases, hypertension and
atherosclerosis which is the primary cause of life-threatening diseases such as, stroke and myocar-
dial-infarction.
Conclusion: PDEs are used to synthesize modified oligonucleotides, which are useful in potential
therapeutic applications. Characterization of PDEs from different snake venoms has potential in
identifying new anticoagulants that target specific active sites, which leads to the treatment of hae-
mostatic disorders. Here, we review the snake venom PDEs potential therapeutic activity against
platelet aggregation which could provide ideal platforms to design drugs for treatment or to fight

against unwanted clots formation.

Keywords: PDEs, cAMP, cGMP, ADP, oligonucleotides, platelet aggregation.

1. INTRODUCTION 1.1. Venomous Snakes Families

Phosphodiesterase (PDEs) are enzymes that are used to
disrupt phosphodiester bonds. These are glycoproteins and
are membrane bound. The hydrolysis of various nucleotide
polyphosphates is catalysed by theses enzymes. Phosphodi-
esterase-I is used in phosphodiesterase activation assays to
hydrolyze AMP.
Cocktails of purely dynamic gears of biology, snake ven-
oms consist of carbohydrates, free amino acids, lipids, pro-
teins, peptides, toxins and hydrolytic enzymes, proteins and
peptides which are non-enzymatic, inorganic cation and or-
ganic components used for both the immobilization and di-
gestion of prey [1].The most common enzymes in snake
venoms are serine proteinases, Phospholipase A2s (PLA2s),
acetylcholinesterases (AChEs), metalloproteinases, L-amino
acid oxidases, hyaluronidases, phosphodiesterases, nucleoti-
dases (5’-nucleotidases, ATPases and DNases) [2]. Phos-
phodiesterase, DNase, and RNase are those hydrolytic en-
zymes, which are universally present in all venoms of
snakes, but their pharmacological activities were less charac-
terized during early studies [3-5].
*Address correspondence to this author at the Department of Pharmaceutics,
Faculty of Pharmacy, Gomal University, Dera Ismail Khan 29050, Khyber
Pakhtunkhwa, Pakistan; Mob No: +92-333-9732578;
Tel/Fax: +92-966-750284; E-mail: barki.gold@gmail.com
1875-5305/18 $58.00+.00
Until now, 600 species of these venomous snakes are
known, one fourth of species of snakes are further classified
into these families: Crotalidae, Colubridae, Hydrophidae,
Atractaspididae, Viperidae [6].
1.2. Nucleases
Nucleases are that type of enzymes which act on nucleic
acids comprising of DNA and RNA. The nucleases present
in snake venom consist of exonucleases and endonucleases.
Endonucleases are further classified in DNases and RNases,
DNA is hydrolyzed by DNases, and RNA is hydrolyzed by
RNases. On the other hand, Exonucleases consists of Phos-
phodiesterases (PDE), which has role in the hydrolysis of
both DNA and RNA [7, 8].
1.3. Differentiation of Phosphodiesterases from Endonu-
cleases
It is a difficult task to differentiate between the specific
activity of venom endonuclease and PDE because endonu-
cleolytic activity is snake venom PDE’s inherent property
[9]. For the differentiation of PDE from endonucleases, other
biochemical parameters are also needed along with substrate
specificities. Venom proteins having an optimum acidic pH
and that do not require any divalent cation to hydrolyze
DNA / RNA is considered as endonuclease [5] while all oth-
© 2018 Bentham Science Publishers
Phosphodiesterases (PDEs) from Snake Venoms
ers are PDEs that require divalent metal ion and basic pH for
their enzymatic activity [4, 5]. Almost all PDEs become ac-
tive at basic pH and their further activity requires divalent
metal ion [4, 5]. The DNase activity of phosphodiesterase
has also been reported by Sittenfeld [10] and this activity
was calculated at pH 7.0 by utilizing the DNA of calf thy-
mus. A research study by de Roodt et al. [11] showed that
activity on plasmid and DNA of calf thymus in zymogram is
because of DNase [9]. Current research study conducted by
de Roodt et al. [11] showed that DNase activity on calf thy-
mus DNA and plasmid in zymogram is due to PDE instead
of DNase because EDTA inhibited the activity [9].
1.4. PDEs (EC 3.1.4.1) Function
PDEs play diverse roles in metabolic processing of ex-
tracellular nucleotides and also regulate nucleotide-based
intercellular signalling [12]. It is observed that PDEs form 11
heterologous families [13].
1.5. PDEs Mechanism of Action
PDEs catalyze the process of hydrolysing phosphodiester
bonds in a progressive way that begins at the 3′-end of
polynucleotides and releases 5′=mononucleotides at basic pH
(Figure 1). PDEs action has been observed against large va-
riety of snake taxonomy and found distributed in snake ven-
oms [4, 5, 14, 15].
DNA/RNA
Phosphodiesterase
5'AMP, , 5'TMP, 5'GMP
5'CMP, 5'UMP
Figure 1. Hydrolysis of DNA/RNA by snake venom phosphodi-
esterases liberating 5′mononucleotides.
Viperid and Crotalid venoms have higher PDE activity as
compared to elapid venoms [3, 5]. It is shown in different
studies that PDEs act on various native substrates like DNA,
rRNA, tRNA and show no preference for pyrimidine or
purine bases. Native DNA acts as a better substrate as com-
pared to denatured DNA [4] as these enzymes hydrolyze the
oligonucleotides that are polyadenylic acid and cyclic nu-
cleotides (Figure 2) [16]. Extracellular PDEs are exonucle-
ases, which are present in venoms and cause envenomation
by attacking nucleic acids by removing mononucleotide from
the polynucleotide chain in a stepwise way [17, 18]. PDEs
also possess the endonucleolytic action guided towards sin-
gle-stranded DNA [19, 20] and they have also been used for
the sequencing of polynucleotides and oligonucleotides [21].
Protein & Peptide Letters, 2018, Vol. 25, No. 7 613
PDE
Figure 2. Hydrolysis of 3’, 5’-cAMP by venom phosphodiesterase.
Enzyme action (arrow) typically liberates 5’-AMP [5].
In addition, PDE also hydrolyzes TDP-rhamnose, UDP-
glucose, GDP-mannose, adenosine 5′-tetraphosphate, NAD+,
NADP+, poly (ADP) ribose and different other derivatives
of nucleic acid [4]. Furthermore, PDEs also hydrolyze ADP
and ATP, releasing adenosine [5, 22]. ADP is secreted from
the platelets as dense granules by various agonists and is a
potent inducer of platelet aggregation. Logically, hydrolysis
of ADP should lead to inhibition of platelet aggregation. It
was concluded that generation of adenosine as a result of
ADP removal by PDE was responsible for inhibitory effect
in aggregation of platelets [23].
1.6. PDEs Characteristics
Snake venom PDEs have been extracted and character-
ized from venoms of various snake species. The properties of
various isolated venom PDEs are presented in Table 1. Gen-
erally, as compared to RNases, usually PDEs have higher
molecular mass (>90 kDa) and are single polypeptide chain
proteins. Existence of a few PDEs as homodimers is also
reported by different researchers [7, 22, 24]. These can be in
multi molecular forms or just in one form [7, 16, 25]. All
metalloenzymes of PDEs generally contain the activity of
PDEs [4, 5, 26, 27].
According to Mori et al. Crotalus ruber PDE contained
1.04 M zinc/M of enzyme. In addition, at higher concentra-
tion Zinc acts as inhibitory agent [7, 28, 29]. Zinc is respon-
sible for catalysis, while calcium and magnesium are essen-
tial for substrate binding [30].
Recently Katrin et al. cloned and sequenced the cDNA
that encodes PDE from Vipera lebetina resulting in 2772
nucleotides sequence with an ORF consisting of 2556 nts.
The protein translated comprised of 851 amino acids includ-
ing a signal peptide of 23-amino acid. VLPDE is initially
translated as a single chain protein of 828 amino acids but
subsequently for the formation of a two-chain protein as end
product, bridged together through disulphide bonds. Under
reducing environment this enzyme behaved as heterodimeric
protein and quite differently from other real heterodimers. It
is translated as a single-chain protein. It is the first snake
venom PDE with confirmed and well established primary
structure (Figure 3). The VLPDE having (molecular mass
~120 kDa) hydrolyses ADP but not 5’-AMP and ATP. Its
optimum pH falls in the pH range between 8.5 and 9.0. Its
activity was reported highest at 60°C, activity decreases if
614 Protein & Peptide Letters, 2018, Vol. 25, No. 7 Uzair et al.

Table 1. Properties of Phosphodiesterases Purified from different Snake Venoms.

Snake (PDE) Substrate MM Inhibitor References

kDa

B. atrox polyA, Bis-pNPP 130 EDTA [16]

B. alternates Bis-pNPP 105 --"-- [29]

Cerastes cerastes --"-- 110 EDTA, cysteine, [50]

Crotalus adamentus --"-- 115, 140 AMP, ADP [8]

Cr. mitchilli pyrrhus cAMP, ATP, ADP 110 EDTA [22]

Cr. rubber rubber Bis-pNPP 98 PCMB, EDTA [7]

Cr. viridis oreganus DNA/RNA, cAMP 114 EDTA [24]

Trimeresures flavo-viridis --"-- 140 --"-- [25]

T. mucrosquamatus DNA/RNA ------ EDTA, PCMB [28]

Bothrops jararaca (Nn-PDEII) ADP 228 dithiothreitol and EDTA [47]

Trimeresurus Stejnegeri (TS-PDE) ATP,NAD,ADP 100 ------- [35]

Daboia russelli russelli (DR-PDE) ADP ------- Metal chelators [12]

Vipera lebetina (VL-PDE) ADP 120 ------ [31]

Naja nigricollis (Nn-PDEII) - 125 EDTA [40]

DTT
Note: Bis-pNPP: bis-p-nitrophenyl phosphate; PCMB: p-chloromercuribenzoate

heated at 65°C. However, about 25-30% of its activity is

reported at 100°C also. It is a relatively thermostable en-
zyme. VLPDE protein consists of four domains: a nonspe-
cific endonuclease domain, a PDE/nucleotide pyrophospha-
tase domain and two somatomedin-B domains (Figure 4)
[31].
Previously PDEs were isolated from several venoms, but
there was no information given regarding cDNA or amino
acid sequences. Expressed Sequence Tag (EST) sequences
(Accession Number: S. catenatus edwardsii, DY587965.1: L.
Muta, DY403207, DY403416: D. Acutus, DV561486,
DV563305) [32, 33] generated using cDNA library of Sistru-
rus catenatus edwardsi, Lachesis muta, and Deinagkistro-
don acutus species are reported to be representatives of the
PDE gene [33, 34].
1.7. PDEs Importance
PDEs influence has been observed in a vast majority of
pharmacological processes like cell differentiation, proin-
flamatory mediator production and function, learning, apop-
tosis, muscle contraction, ion channel function, lipogenesis,
gluconeogenesis and glycogenolysis. With diverse physio-
logical functions, PDEs are becoming new therapeutic tar-
gets for the treatment of different diseases [35]. Enormous
number of membrane proteins are targeted by these sub-
stances and receptors, selectivity and potency, high affinity
coagulating proteins, showing potential for designing of
drugs to understand the mechanism of action of complex
venom proteins for the development of novel drugs and
therapies to treat serious diseases like hypertension, throm-
bosis, arthritis, heart diseases, infections caused by microbes,
cancer, huge consideration has been given, during the recent
years [35].

1.8. Snake Venom PDEs

Figure 3. Predicted 3D-structure of VLPDE (without signal pep-
tide), generated by Phyre server. C denoting C-terminus while N
denoting N-terminus of protein [31].
Snake venoms PDEs are largely distributed amongst sev-
eral snake texa, only few researchers have investigated bio-
logical activities of these ubiquitous venom components. As
shown by Russell et al. [36] in earlier research, a drop occurs
in mean arterial pressure and also a reduction in locomotors
depression with partially purified PDE preparation from
various snake venoms. These effects can be due to a drop in
cAMP levels. As reported this preparation was contaminated
with other proteins, still the results were noteworthy and
significant because it was indicated that even in absence of a
Phosphodiesterases (PDEs) from Snake Venoms
1 125 250
Query seq.
Specific hits
Superfamilies Somatom Somatom Sulfatase superfamily
Multi-domains Phosphodiest
Figure 4. PDE different domains: according to the NCBI-BLAST.
cellular disruption there was adequate substrate availability
for the PDE in circulatory system that resulted in hypoten-
sion. Furthermore, PDEs possess the ability to hydrolyze a
wide range of biologically important nucleotides such as
NADP+, NAD +, GDP, and ATP. However, PDEs have not
been investigated for other potential pharmacological activi-
ties [9].
Previously toxicologists showed less interest in these
enzymes because of their only involvement in digestion and
no other toxicological activities, so are less characterized for
their pharmacological activities [3, 4, 5].
2. SNAKE VENOM PDEs IN THERAPEUTICS
Recently, toxicologists showed an improved interest in
these enzymes, because these enzymes have functions to
liberate endogenously, so, these are responsible to work like
multi-toxins [3, 20]. Thermal stability, higher catalytic effi-
ciency, and resistance to proteolysis make these enzymes
attractive models for structural biologists, biochemists, en-
zymologists for the treatment of various diseases like erectile
dysfunction, inflammatory diseases, Alzheimer’s disease,
cardiac and vascular associated diseases [35].
Researchers reported that enzymes in snake venoms have
an intriguing phenomenon both from a biological and chemi-
cal point of view. These proteins have the potential to modu-
late the physiological reactions by envenomated animals,
hence these make an obvious promise as prospective phar-
macological tools and drug leads. PDEs are particularly at-
tractive for researchers in the field of pharmacology [37-39].
The field of PDE research advanced the development of new
drugs for atherosclerosis which is increasing at an alarming
rate [40].
2.1. Snake Venom PDEs in Oligonucleotides Synthesis
PDEs endonucleolytic activities towards single-stranded
DNA have been used for sequencing oligonucleotides and
polynucleotides [8, 41-43].
Recently, Matsuda has utilized the snake venom phos-
phodiesterase in the development of highly nuclease-
resistant chemically adapted therapeutic oligonucleotide
[44]. PDEs are used in therapeutic oligonucleotide analogues
synthesis. Replacement of the normal phosphodiester inter-
sugar linkages found in natural oligomers having four atoms
linked with groups, form unique di- and poly-nucleotides and
nucleosides useful to regulate RNA expression and therapeu-
Protein & Peptide Letters, 2018, Vol. 25, No. 7 615
375 500 625 750 851
active site
M92+ binding site
Substrate binding site
NUC
NUC superfamily
Endonuclease_NS
tics. Method of therapeutic oligonucleotide synthesis have
also been disclosed [45].
PDE activity is recognized from the venoms of many
snakes. It has been recovered from a number of venom-gland
transtriptome libraries, including those of elapid snakes [46]
and viperid snakes (such as Sistrurus catenalus edwardsii)
[32].
2.2. Snake Venom PDEs Anticoagulant Therapeutic Ac-
tivity in Platelet Aggregation
With an alarming increase in arthrosclerosis that leads to
life threatening disease like myocardial infarction and
strokes, scientists and researchers are looking for highly spe-
cific and potent anticoagulants for the treatment of these
deadly diseases. Snake venom PDEs therapeutic potential
against platelet aggregation provides alternate highly specific
and potent anticoagulants for the treatment of these diseases
[40].
2.3. PDE from Bothrops jararaca Snake Venom
Santoro et al. isolated and functionally characterized a
soluble phospho-diesterase from venom of Bothrops jara-
raca, which showed amino acids sequence resemblance to
mammalian Nucleotide Pyrophosphatase/Phosphodiesterase
3 (NPP3). This enzyme is reported to inhibit platelet aggre-
gation induced by ADP. This has a 228 kDa molecular mass
estimated by size exclusion chromatography. NPPBJ exhibits
nuclease, phosphatase and pyrophosphatase activities, pref-
erably hydrolyzes the nucleoside 5′-triphosphates over nu-
cleoside 5′-diphosphates. It was not activated upon nucleo-
side 5′-monophosphates. Based on substrates used, dithio-
threitol and EDTA inhibited the NPP-BJ catalytic activity
differently. ADP induced platelet aggregation was also abol-
ished by NPP-BJ, but platelet aggregation induced by throm-
bin was slightly attenuated. Polyclonal antibodies produced
against NPP-BJ enzyme did not eradicate the snake B. jara-
raca venom lethal activity. Results showed interference of
NPP-BJ with mechanisms of platelet aggregation induced by
ADP [47].
2.4. PDE-I from Agistrodon bilineatus Snake Venom
In 2009 S.S. Al-Saleh et al purified Phosphodiesterase I
(PDE-I, EC 3.1.4.1) from Agistrodon bilineatus snake
venom having a molecular mass of 140 kDa. The results
showed that β -mercaptoethanol treatment did not changed
616 Protein & Peptide Letters, 2018, Vol. 25, No. 7
the location of the band; this signifies that protein has no
subunits. There were no alkaline phosphatase and 5’-
nucleotidase activities in the enzyme. Its optimum pH range
is 9.0-11.0 and optimum temperature is 60ºC. Its activity
decreases at >65ºC. PDE-I is glycoprotein with carbohydrate
content of 14%. Non-competitive inhibition is caused by
cysteine with a Ki=6.3×10−3 M (IC50 of 1.6 mM) and com-
petitive inhibition was caused by ADP. EDTA, zinc, o-
phenanthroline and Glutathione inhibited the enzyme activity
and Mg2+ potentiated the PDE-I enzyme activity slightly.
Thymidine 5’-monophosphate p-nitro-phenyl ester is most
readily hydrolyzed (10-fold) by this enzyme and 3’-5’-cAMP
substrate is hydrolyzed least readily. In mice the concentra-
tion of enzyme up to 4.0 mg/Kg i.p. was not found to be le-
thal. Anticoagulant effect is exhibited and also increased the
normal clotting time of normal citrated plasma of human,
whereas crude venom exhibited strong coagulant effect [48].
2.5. PDE-1 from King Cobra (Ophiophagus hannah)
Venom
S.U. Khan et al. (2009) have purified PDE-1 from O.
Hannah having molecular mass 148 kDa. The enzyme is free
from alkaline phosphatase and 5’-nucleotidase activities. The
enzyme indicated an optimum pH of 10.0 in Tris-HCl buffer.
The optimum temperature was found to be 50ºC. The PDE-1
is a glycoprotein and exhibited basic pI. Cysteine caused a
non-competitive inhibition. The Adenosine Diphosphate
(ADP) caused a competitive inhibition. Glutathione, o-
phenanthroline, Zinc and EDTA inhibited the PDE-1 activ-
ity, whereas magnesium slightly potentiated the activity. The
enzyme hydrolyzed thymidine 5’-mono phosphate p- nitro-
phenyl ester most readily (10 fold) while cyclic 3’-5’-AMP
was least readily hydrolyzed substrate. The PDE-1 up to 4.0
mg/Kg i.p. was not lethal in mice. The PDE-1 exhibited an
anticoagulant effect whereas the crude venom showed strong
coagulant effect [49].
2.6. PDE I from Walterinnesia aegyptia Venom
Al-Saleh et al purified PDE-I from Walterinnesia aegyp-
tia venom in 2011. It has a molecular mass of 158 kD. It is
single chain glycoprotein. The enzyme was free of alkaline
phosphatase and 5'-nucleotidase activities. Its optimum pH is
9.0 and optimum temperature is 60°C. Non-competitive in-
hibitor is cysteine with Ki = 6.2 × 10-3 M and an IC50 of 2.6
mM and competitive inhibitor is adenosine diphosphate.
Zinc, o-phenanthroline, Glutathione and EDTA inhibited
PDE-I activity whereas Mg2+ presence potentiated the activ-
ity slightly. thymidine-5'-monophosphate p-nitrophenyl ester
was most readily hydrolysed by, whereas cyclic 3'-5'-AMP
was least susceptible to hydrolysis by PDE-I. In mice PDE-I
at a dose of 4.0 mg/kg was not found to be lethal but on hu-
man plasma it exhibited an anticoagulant effect. It is clear
from these findings that PDE-I from W. aegyptia shares
various features with this enzyme isolated from other differ-
ent snakes’ venom [45].
2.7. TS-PDE from Trimeresurus stejnegeri Snake Venom
Lili et al. isolated and partially characterized a novel
PDE, named TS-PDE, from T. stejnegeri venom. It is a gly-
coprotein with 2.48% carbohydrates. It is heterodimer with
Uzair et al.
disulphide linkage and, having 100 kDa molecular mass and
isoelectric point of 5.1, respectively. Among all reported
PDEs, TS-PDE is the only PDE that accommodates both of
endogenous Zn2+ and Cu2+ (essential for its phosphodi-
esterase activity). The purified TS-PDE exhibited wide PDE
substrates range. The specificity order is: nicotinamide gua-
nine dinucleotide > ATP > NAD > ADP. It showed exonu-
clease property with no contamination of either 5′-
nucleotidase or alkaline phosphatase activity. It is reported to
strongly inhibit platelet aggregation induced by ADP in hu-
man platelet-rich plasma by ADP hydrolysis. Novel TS-PDE
is a unique PDE having different structure from all well-
known PDEs [35].
2.8. Dr-PDE from Daboia russeli russelli Snake
Mitra and Bhattacharyya in 2014 purified Daboia russeli
russelli (Dr-PDE) PDE from Russell’s viper venom. It was
inactivated by metal chelators and polyvalent anti-venom
serum. DR-PDE hydrolyzed ADP and inhibited platelet ag-
gregation induced by ADP in platelet rich plasma of human
[12].
2.9. VLPDE from Vipera lebetina Snake Venom
Katrin et al. in 2014 isolated, characterized and eluci-
dated the structural properties of a phosphodiesterase from
Vipera lebetina venom (VLPDE). Cloning and sequencing
studies showed that cDNA encoding VLPDE is consist of a
sequence of 2772 nt (nucleotides) having an ORF consist-
ing of 2556 nt and translated product is comprised of a total
of 851 amino acids together with a signal peptide comprised
of 23-amino acids. It is translated as a single chain protein of
828-amino acid and subsequent cleavage leads to form a
protein with two-chains held together through disulfide link-
ages. Enzyme under reducing environment behaved as a het-
erodimeric protein quite differently as compared to other real
heterodimers. It is the first snake venom PDE with con-
firmed and well established primary structure. The VLPDE
with a molecular mass of 120 kDa, hydrolyses only ADP,
but not ATP and 5’AMP and induction of aggregation of
platelets by collagen or ADP is inhibited by VLPDE dose
dependently [31].
2.10. Nn-PDEII from Naja nigricollis Snake Venom
Ibrahim et al. carried a study in 2016 and reported that
Phosphodiesterase (PDE) enzymatic activity was screened in
four Egyptian snake venoms belonging to families Elapidae
and Viperadae and a highly active enzyme (Nn-PDEII), from
the richest snake venom species Naja nigricollis. It was puri-
fied in a set of immunological, biochemical and biological
assays. Purification was followed in two successive steps
including gel filtration and ion exchange chromatography.
The enzyme exists as a dimer with a disulphide bridges be-
tween the two subunits. The enzyme showed its optimum
activity at 60ºC and pH 8. As it is best stable in alkaline me-
dium (pH 8-9) at 40ºC up to 1 h, however, it loses ~50%
activity markedly increased by Co+2, Mn+2 and Mg2+, in-
creased to a lesser extent by Ni2+, K+, Ca2+, Ba2+, and Na+ but
not significantly affected by Zn2+ ions and iodoacetic acid.
Al3+ and Cu2+ ions, PMSF, DTT, EDTA, O-phenanthroline
and L-cysteine exhibited obvious inhibitory effects. Nn-
Phosphodiesterases (PDEs) from Snake Venoms
PDEII was highly immunogenic to rabbits and induce anti-
bodies specific to N. nigricollis venom antigens. In addition,
anti-PDEII antibodies were able to partially neutralize, in
vitro, PDE activity of the enzyme in a dose dependent man-
ner. Nn-PDEII exhibited potent anticoagulant effect most
probably via inhibiting one or more of the coagulation fac-
tors within the intrinsic pathway in the coagulation cascade
and exhibited as a potent anticoagulant, by prolonging the
partial thromboplastin time especially at higher concentra-
tions of Nn-PDE [40].
CONCLUSIONS
In conclusion the potential therapeutic characteristic ap-
plications have been reviewed. Such studies could have me-
dicinal or pharmacological impact and could open doors for
further studies for identifying new drug leads from deadly
snake venoms. With the increasing risk of atherosclerosis
which is the primary cause of life-threatening diseases such
as, stroke and myocardial infarction, particularly among in-
creasingly aged population throughout the world. Search for
new anticoagulants that mark specific active sites are becom-
ing essential. The biodiversity of snake venom PDEs that
affect blood coagulation have been attractive sources for new
lead compounds for treatment of thromboembolic disorders.
CONSENT FOR PUBLICATION
Not applicable.
CONFLICT OF INTEREST
The authors declare no conflict of interest, financial or
otherwise.
ACKNOWLEDGEMENTS
Declared none.
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