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PDBsum entry 2zm4
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References listed in PDB file
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Key reference
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Title
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The importance of ch/pi hydrogen bonds in rational drug design: an ab initio fragment molecular orbital study to leukocyte-Specific protein tyrosine (lck) kinase.
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Authors
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T.Ozawa,
E.Tsuji,
M.Ozawa,
C.Handa,
H.Mukaiyama,
T.Nishimura,
S.Kobayashi,
K.Okazaki.
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Ref.
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Bioorg Med Chem Lett, 2008,
16,
10311-10318.
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PubMed id
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Abstract
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The interaction energy was calculated, by the ab initio FMO method, for
complexes between LCK protein and four inhibitors (staurosporine, BMS compound
2, and our compounds 3 and 4). In every case a number of CH/pi hydrogen bonds
have been disclosed in the so-called adenine pocket. In complexes of 2, 3, and
4, CH/pi and NH/pi hydrogen bonds have been observed in another pocket. In view
of the above results, the aniline ring of 3 was replaced by 2,6-dimethyl aniline
to increase the potency for LCK kinase. A 10-fold increase in the potency has
been achieved for 4 over 3. We suggest that the concept of weak hydrogen bonds
is useful in the rational design of drugs.
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