Biomedical Engineering Reference
In-Depth Information
Nucleosides
O
NH
2
O
NH
2
O
O
HN
N
CH
3
N
N
HN
N
N
NH
NH
O
N
HOHC
2
O
N
HOHC
2
O
N
N
O
N
HOHC
2
N
N
HOHC
2
N
O
N
NH
2
O
O
HOHC
2
HOHC
2
O
O
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
Adenosine
Guanosine
Inosine
Thymidine
Cytidine
Uridine
Nucleobases
NH
2
O
O
NH
2
O
O
H
3
C
N
N
N
N
NH
NH
N
NH
NH
NH
NH
NH
O
N
N
NH
2
NH
NH
O
NH
O
N
Adenine Guanine
Hypoxanthine Thymine Cytosine Uracil
Selected Nucleoside Analogs Used as Drugs
NH
2
O
O
NH
2
N
CH
3
HN
HN
N
NH
N
Cl
N
N
O
N
HOH
2
C
N
O
HOH
2
C
O
N
N
O
HOH
2
C
HOH
2
C
O
O
N
3
OH
ddC ddI AZT Cladribine
NH
2
NH
2
NH
2
O
N
N
N
H
2
N
N
N
N
N
N
O
N
HO
N
HOH
2
C
O
N
F
O
HOH
2
C
O
HOH
2
C
O
O
HO
F
OH
OH
HO
F
OH
OH
HO
Ribavirin
Ara-C
Gemcitabine
Fludarabine
FIGURE 8.1.
Structures of selected nucleosides and nucleoside analogs.
effects on many tissues and organs by activating specific purinergic receptors.
1
,
2
Nucleosides are hydrophilic and have low membrane permeability. To facilitate the
movement of nucleosides across cell membranes, mammalian cells have evolved two
major classes of transporters: concentrative nucleoside transporters (CNTs) and equi-
librative nucleoside transporters (ENTs). At the cellular level, these transporters play
key roles in salvaging nucleosides for DNA and RNA syntheses and in regulating
adenosine signaling at the receptor sites. From a whole-organism point of view, nu-
cleoside transporters expressed in absorptive and excretory organs are important for
maintaining total body homeostasis of nucleosides. The pharmacological significance
of nucleoside transporters originates from the wide use of nucleoside analogs in the
treatment of cancer, viral infections, and other pathophysiological conditions. The
structures of a few clinically used nucleoside analogs are shown in Figure 8.1. Many
of the therapeutic nucleoside analogs rely on nucleoside transporters to enter or exit
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