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not only towards ADA, but also towards A1R (Ki
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14, 18 and 19 for A1 adenosine receptors and the
stereoselectivity of compounds 6, 14 (Ki erythro 6/Ki
threo 6 0.42, Ki erythro 14/Ki threo 14 0.16) and of other
2-hydroxynonyl compounds reported in the literature
(for example, EHNA and THNA [26], 1-(2-hydroxy-3-
nonyl)-1,2,4-triazole-3-carboxamides [28] or 2-hydroxy-
3-nonylderivatives of azoles [29]) for ADA, we can
observe that, towards the two proteins, erythro com-
pounds are more active than threo ones.
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This indicates that the moieties of the two proteins
which bind the N(9) substituent (pocket II) could have
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6. Conclusions
Adenosine is the endogenous ligand of ADA protein
and of A1 receptor protein. In the past we have ob-
served that these proteins could recognise some ana-
logues of adenine and adenosine through favourable
interactions with them, specially with reference to ADA
obtained from cow milk and A1 protein from cow
brain.
Results in this work show that two similar zones and
one different zone between the three dimensional struc-
tures of the binding site of the two proteins could be
present.
In fact the zones facing both the 2 position and the 9
position of the adenosine nucleus presented some
analogies. Introduction of an aromatic group, in partic-
ular a phenyl one, on the 2 position and of the 3-(2%-hy-
droxynonyl) chain on the 9 position, leads to products
with improved affinities towards ADA and A1 receptor
proteins. Therefore, these two zones should present
similar binding characteristics, in spite of having diffe-
rent aminoacidic sequences. Instead, the third zone
facing the N6 position presents great differences: ADA,
as is known, does not accept any substituent except
methyl [30], whereas A1 protein can bind bulky groups
such as cycloalkyl ones.
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A
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