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.com
Volume 7, Issue 5 (Suppl)
J Biotechnol Biomater
ISSN: 2155-952X JBTBM, an open access journal
Biotechnology 2017
November 13-14, 2017
November 13-14, 2017 Osaka, Japan
19
th
World Congress on
Biotechnology
J Biotechnol Biomater 2017, 7:5 (Suppl)
DOI: 10.4172/2155-952X-C1-083
Pharmacoinformatic approach for discovery of better drug combination with currently available drug
against Leishmaniasis
Md Yousuf Ansari
MM University, India
H
ypoxanthine phosphoribosyl transferase (HGPRT; EC 2.4.2.8) is a central enzyme in the purine recycling pathway of
all protozoan parasites. Protozoan parasites cannot synthesize purine bases (DNA/RNA) which is essential for survival
as lack of de novo pathway. Thus, its good target for drug design and discovery as inhibition leads to cessation of replication.
PRTase (transferase enzyme) has common PRTase type-I folding pattern domain for its activities. Genomic studies revealed
the sequence pattern and identified highly conserved residues catalyzed the reaction in protozoan parasites. A recombinant
protein has 24 kDa molecular mass (rLdHGPRT) was cloned, expressed and purified for testing of guanosine monophosphate
(GMP) analogous compounds
in vitro
by spectroscopically to the rLdHGPRT, Lysates protein and MTT assay on
Leishmania
donovani
. The predicted inhibitors of different libraries were screen into FlexX. The reported inhibitors were tested
in vitro
.
The 2’deoxyguanosine 5’ diphosphate (DGD) (IC
50
value 12.5 μM) is two times more effective when compared to guanosine-5’
diphosphate sodium(GD). Interestingly, LdHGPRT complex has showed stable after 24ns in molecular dynamics simulation
with interacting amino acids are Glu125, Ile127, Lys87 and Val186. QSAR studies revealed the correlation between predicted
and experimental values has shown R
2
=0.985. Concludes that inversely proportional to their docked score with activities. It is
predicted that patients suffering from both HIV and visceral leishmaniasis (VL) may benefit if they are treated with acyclovir
in conjunction with first-line anti-leishmanial therapies such as Miltefosine and AmBisome.
yousufniper@mmumullana.org