Said, Ahmed M. published the artcileBinding cooperativity between a ligand carbonyl group and a hydrophobic side chain can be enhanced by additional H-bonds in a distance dependent manner: A case study with thrombin inhibitors, Application of (R)-tert-Butyl (3-methyl-1-oxobutan-2-yl)carbamate, the publication is European Journal of Medicinal Chemistry (2015), 405-424, database is CAplus and MEDLINE.
One of the underappreciated non-covalent binding factors, which can significantly affect ligand-protein binding affinity, is the cooperativity between ligand functional groups. Using four different series of thrombin inhibitors, we reveal a strong pos. cooperativity between an H-bond accepting carbonyl functionality and the adjacent P3 hydrophobic side chain. Adding an H-bond donating amine adjacent to the P3 hydrophobic side chain further increases this pos. cooperativity thereby improving the Ki by as much as 546-fold. In contrast, adding an amidine multiple H-bond/salt bridge group in the distal S1 pocket does not affect this cooperativity. An anal. of the crystallog. B-factors of the ligand groups inside the binding site indicates that the strong cooperativity is mainly due to a significant mutual reduction in the residual mobility of the hydrophobic side chain and the H-bonding functionalities that is absent when the separation distance is large. This type of cooperativity is important to encode in binding affinity prediction software, and to consider in SAR studies.
European Journal of Medicinal Chemistry published new progress about 106391-88-2. 106391-88-2 belongs to esters-buliding-blocks, auxiliary class Amine,Aliphatic hydrocarbon chain,Amide,Aldehyde, name is (R)-tert-Butyl (3-methyl-1-oxobutan-2-yl)carbamate, and the molecular formula is C10H19NO3, Application of (R)-tert-Butyl (3-methyl-1-oxobutan-2-yl)carbamate.
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