Protein-Ligand Interactions: Thermodynamic Effects Associated with Increasing the Length of an Alkyl Chain.

ABSTRACT: 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 analogs. 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 hav

SUBMITTER: Myslinski JM 

PROVIDER: S-EPMC3859442 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature