Human ligand-derived models

Irreversible inhibition is probably due to the alkylation of a histidine residue.43 Chymotrypsin is selectively inactivated with no or poor inhibition of human leukocyte elastase (HLE) with a major difference the inactivation of HLE is transient.42,43 The calculated intrinsic reactivity of the coumarin derivatives, using a model of a nucleophilic reaction between the ligand and the methanol-water pair, indicates that the inhibitor potency cannot be explained solely by differences in the reactivity of the lactonic carbonyl group toward the nucleophilic attack 43 Studies on pyridyl esters of 6-(chloromethyl)-2-oxo-2//-1 -benzopyran-3-carboxylic acid (5 and 6, Fig. 11.5) and related structures having various substituents at the 6-position (7, Fig. 11.5) revealed that compounds 5 and 6 are powerful inhibitors of human leukocyte elastase and a-chymotrypsin thrombin is inhibited in some cases whereas trypsin is not inhibited.21... 

F1GURE 5-22 Structure of a human class I MHC protein, (a) This model is derived in part from the known structure of the extracellular portion of the protein (PDB ID 1 DDH). The a chain of MHC is shown in gray the small /3 chain is blue the disulfide bonds are yellow. A bound ligand, a peptide derived from HIV, is shown in red. (b) Top view of the protein, showing a surface contour image of the site where peptides are bound and displayed. The HIV peptide (red) occupies the site. This part of the class I MHC protein interacts with T-cell receptors. 

Vianna EP, Ferreira AT, Dona F, Cavalheiro EA, Silva Fernandes MJ (2005) Modulation of seizures and synaptic plasticity by adenosinergic receptors in an experimental model of temporal lobe epilepsy induced by pilocarpine in rats. Epilepsia 46(Suppl 5) 166-173 Volpini R, Costanzi S, Lambertucci C, Taffi S, Vittori S, Klotz KN, Cristalli G (2002) N(6)-alkyl-2-alkynyl derivatives of adenosine as potent and selective agonists at the human adenosine A(3) receptor and a starting point for searching A(2B) ligands. J Med Chem 45(15) 3271-3279... 

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