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conferenceseries
.com
Volume 5, Issue 3 (Suppl)
J Infect Dis Ther, an open access journal
ISSN:2332-0877
Infectious Diseases 2017
August 21-23, 2017
3
rd
Annual Congress on
Infectious Diseases
August 21-23, 2017 San Francisco, USA
In vivo, in vitro
interaction of silver nanoparticles with leucine amino peptidase from human and
Plasmodium falciparum
Chris Whiteley
Rhodes University, South Africa
Statement of the Problem
: There is increasing requirement for the development of new drug protocols against malaria, a fatal
disease caused by the lethal parasite
Plasmodium falciparum
. Leucine aminopeptidase (PfLAP) of
Plasmodium falciparum
is
being pursued as a promising target for the discovery of novel antimalarials.
Methodology:
Pf
LAP and HsLAP were expressed in
Escherichia coli
, and AgNPs (3-10 nm) characterized by ultra-violet
spectroscopy and transmission electron microscopy. The effects of silver nanoparticles (AgNPs) against
P. falciparum
leucine
amino-peptidase (PfLAP) and the human homolog (HsLAP) were compared.
Findings:
PfLAP indicated a K
m
of 694 µM towards leucine-
p
-nitroanilide and a V
max
of 57.9
μmol.ml-1
. min
-1
while
Hs
LAP
had a Km of 1.6 mM and V
max
of 119.6
μmol.ml-1.min-1. On interaction with AgNPs (670 nM) PfLAP was selectively inhibited
(57.1 %; K
i
=610 nM) relative to HsLAP (10.8 %; K
i
=5.22 µM). The viability of
P. falciparum
parasites was decreased when
exposed to silver nanoparticles, with an IC
50
value of 6.96 μM, compared to an IC
50
value of 647.7 μM for human HeLa cells.
Conclusion & Significance:
Structural differences between the enzyme variants, particularly the orientation and distance of
surface Met
349
in PfLAP and Met
306
in HsLAP to the zinc binding sites were significant and may allow for selective targeting of
Pf
LAP by AgNPs.
Biography
Chris Whiteley is an Emeritus Professor of Biochemistry at Rhodes University, Grahamstown, South Africa and distinguished Research Professor at National
Taiwan University Science & Technology, Visiting International Professor in Enzymology at School of Bioscience & BioEngineering of South China University
Technology, Guangzhou, PRC. He served as Visiting Research Scientist at the Department of Chemical Engineering, National Taiwan University, Taipei, Taiwan
in 2004 and as Visiting Professor of Biochemistry at Institute of Biomedical Technology, Veterans General Hospital, Yang Ming University, Taipei, Taiwan. He also
worked as Visiting Professor of Enzymology & Organic Synthesis at Oregon State University, Corvallis, Oregon, USA and Visiting Professor of Organic Synthesis
at University British Columbia, Vancouver, Canada. He is the Executive Member of Royal Chemical Society (London), MRSC (C. Chem), South African Chemical
Institute (SACI). He has published 6 chapters in books and has 110 peer-reviewed papers on Biomedical Enzymology and Nanomaterials.
c.whiteley@mail.ntust.edu.twChris Whiteley, J Infect Dis Ther 2017, 5:3 (Suppl)
DOI: 10.4172/2332-0877-C1-026