Low-power laser pulses of 6 ns duration (1064 nm wavelength) have been used to create plasma in an aqueous solution of plasmid DNA (pUC19). Thermal energy electrons and • OH radicals in the plasma induce strand breakages in DNA, including double strand breaks and possible base oxidation/base degradation. The time evolution of these modifications shows that it takes barely 30 s for damage to DNA to occur. Addition of physiologically relevant concentrations of a salt (NaCl) significantly inhibits such damage. We rationalize such inhibition using simple electrostatic considerations. The observation that DNA damage is induced by plasma-induced photolysis of water suggests implications beyond studies of DNA and opens new vistas for using simple nanosecond lasers to probe how ultralow energy radiation may affect living matter under physiological conditions.
Apoptosis is a vital physiological process, which is observed in various biological events. The
anti-apoptotic and pro-apoptotic members of Bcl-2 family are the most characterized proteins which are
involved in the regulation of apoptotic cell death. The anti-apoptotic proteins such as Bcl-2 and Bcl-xL
prevent apoptosis, whereas pro-apoptotic members like Bax and Bak, elicit the release of caspases from
death antagonists inducing apoptosis. Thus, the Bcl-2 family of proteins play a vital role in controlling
programmed cell death. Over expression of anti-apoptotic Bcl-2 proteins are often directly associated
with various kinds of cancer. Developing suitable inhibitors for controlling the elevated levels of these
proteins got much attention in last decade. Structural biology techniques such as Nuclear Magnetic
Resonance (NMR) spectroscopy, X-ray crystallography, homology modeling and molecular docking
play a significant role in identifying the key inhibitors of these proteins. The authors have developed and
tested successfully, several series of indole pharmacore containing inhibitors for Bcl-2 and Bcl-xL proteins
based on the homology modeling, docking and suitable biochemical and apoptosis assays. This
review provides a summary of potential inhibitor molecules developed for Bcl-2 and Bcl-xL proteins, as
well as the the key residues of these proteins interacting with potential drug molecules. The present appraisal
also focuses on the role of computational algorithms in developing potential drug molecules,with
more emphasis on the role of homology modeling and docking studies in developing inhibitors for Bcl-
2, and Bcl-xL proteins in cancer therapy.
Electrons
and •OH-radicals have been generated
by using low-energy laser pulses of 6 ns duration (1064 nm wavelength)
to create plasma in a suspension of plasmid DNA (pUC19) in water.
Upon thermalization, these particles induce single and double strand
breakages in DNA along with possible base oxidation/base degradation.
The time-evolution of the ensuing structural modifications has been
measured; damage to DNA is seen to occur within 30 s of laser irradiation.
The time-evolution is also measured upon addition of physiologically
relevant concentrations of salts containing monovalent, divalent,
or trivalent alkali ions. It is shown that some alkali ions can significantly
inhibit strand breakages while some do not. The inhibition is due
to electrostatic shielding of DNA, but significantly, the extent of
such shielding is seen to depend on how each alkali ion binds to DNA.
Results of experiments on strand breakages induced by thermalized
particles produced upon plasma-induced photolysis of water, and their
inhibition, suggest implications beyond studies of DNA; they open
new vistas for utilizing simple nanosecond lasers to explore the effect
of ultralow energy radiation on living matter under physiologically
relevant conditions.
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