| Autor: |
Stephen F. Martin, John H. Clements, James M. Myslinski, John E. DeLorbe |
| Rok vydání: |
2013 |
| Předmět: |
|
| Zdroj: |
ACS medicinal chemistry letters. 4(11) |
| ISSN: |
1948-5875 |
| Popis: |
Thermodynamic parameters were determined for complex formation between the Grb2 SH2 domain and tripeptides of the general form Ac-pTyr-Xaa-Asn in which the Xaa residue bears a linear alkyl chain varying in length from 1–5 carbon atoms. Binding affinity increases upon adding a methylene group to the Ala derivative, but further chain extension gives no extra enhancement in potency. The thermodynamic signatures of the ethyl and n-propyl derivatives are virtually identical as are those for the n-butyl and n-pentyl analogues. Crystallographic analysis of the complexes reveals a high degree of similarity in the structure of the domain and the bound ligands with the notable exception that there is a gauche interaction in the side chains in the bound conformations of ligands having n-propyl, n-butyl, and n-pentyl groups. However, eliminating this unfavorable interaction by introducing a Z-double bond into the side chain of the n-propyl analogue does not result in an increase in affinity. Increases in the amount o... |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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