Stereoselectivity of binding of alpha-(N-benzylamino)benzylphosphonic acids to prostatic acid phosphatase.
The inhibition effects of enantiomerically pure alpha-(N-benzylamino)benzylphosphonic acids and their derivatives on human prostatic acid phosphatase have been investigated. As expected, (R)-alpha-(N-benzylamino)benzylphosphonic acid demonstrated higher affinity for the enzyme than (S)-enantiomer. At the same time, (1R,2S)-phenyl[(1-phenylethyl)amino]methylphosphonic acid was found to be a significantly weaker inhibitor than its (1S,2R)-analogue. The enantioselectivity has been explained using a molecular modeling approach by computational docking of inhibitors into active center of prostatic acid phosphatase.
Vovk
Andriy I
AI
Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine, Murmanska, 1, 02660, Kyiv-94, Ukraine. vovk@bpci.kiev.ua
Mischenko
Iryna M
IM
Tanchuk
Vsevolod Yu
VY
Kachkovskii
Georgiy A
GA
Sheiko
Sergiy Yu
SY
Kolodyazhnyi
Oleg I
OI
Kukhar
Valery P
VP
D000135:Acid Phosphatase; D001596:Benzylamines / Q000138:chemical synthesis* / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011467:Prostate / Q000187:drug effects / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology*; D011485:Protein Binding; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D013237:Stereoisomerism; D013816:Thermodynamics
D001596:Benzylamines; D063065:Organophosphonates; D011480:Protease Inhibitors; C475503:benzylphosphonic acid; D000135:Acid Phosphatase; C428439:prostatic acid phosphatase; D017027:Protein Tyrosine Phosphatases