Nitric oxide synthases activation and inhibition by metallacarborane-cluster-based isoform-specific affectors.
A small library of boron-cluster- and metallacarborane-cluster-based ligands was designed, prepared, and tested for isoform-selective activation or inhibition of the three nitric oxide synthase isoforms. On the basis of the concept of creating a hydrophobic analogue of a natural substrate, a stable and nontoxic basic boron cluster system, previously used for boron neutron capture therapy, was modified by the addition of positively charged moieties to its periphery, providing hydrophobic and nonclassical hydrogen bonding interactions with the protein. Several of these compounds show efficacy for inhibition of NO synthesis with differential effects on the various nitric oxide synthase isoforms.
Department of Analytical Chemistry, Institute of Chemical Technology in Prague, Technická 5, 166 28 Prague 6, Czech Republic.
Robert
R
Kaplánek
Pavel
P
Martásek
Bohumír
B
Grüner
Satya
S
Panda
Jakub
J
Rak
Bettie Sue Siler
BS
Masters
Vladimír
V
Král
Linda J
LJ
Roman
D001896:Boron Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D003035:Cobalt / Q000737:chemistry*; D006801:Humans; D008956:Models, Chemical; D015394:Molecular Structure; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D020033:Protein Isoforms
D001896:Boron Compounds; D009942:Organometallic Compounds; D020033:Protein Isoforms; D003035:Cobalt; D019001:Nitric Oxide Synthase