Biomedical Engineering Reference
In-Depth Information
5 Perspective
Most currently marketed drugs for cardiac arrhythmias are indiscriminate since that
they all target ion channels especially
h
ERG channel in both atrial and ventricular
myocytes, thus associated with life-threatening ventricular arrhythmias. For medic-
inal chemists, the molecular basis of the ligand-
K
v
1.5
channel interactions and its
specific features should be deeply investigated when aiming at rational design of
atrial-selective drugs.
K
v
1.5
potassium channel is an interesting topic for medicinal chemists in recent
years. Drug targeted cardiac
K
v
1.5
channels may have remarkably selectivity and
safety advantages over current market drugs. Among the residues involved in
ligand-
K
v
1.5
binding, Ile508 and Val512 are equivalent to Tyr652 and Phe656 of
h
ERG channel, thus underlie the possibility of hydrophobic interactions between
blockers and
K
v
1.5
channel. Moreover, the physicochemical property difference
between the hydrophobic residue Ile508 and Val512 of
K
v
1.5
channel and the
aromatic Tyr652 and Phe656 of
h
ERG channel could provide an opportunity in
differentiation of these two channels.
In conclusion, the rapid progress in physiology, pharmacology, biochemistry,
genomics, and proteomics will significantly expedite the investigation of mecha-
nism in cardiac diseases and the development of safe and effective drugs.
Acknowledgement The authors gratefully acknowledge financial support from the National Major
Science and Technology Project of China (Innovation and Development of New Drugs, Grant No.
2008ZX09401-001 and 2009ZX09501-003), National 863 Program (Grant No.2007AA02Z307), and
the Innovation Program for the Postgraduates in Jiangsu in 2007.
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