Binding mechanism of RGD and its mimetics to receptor GPIIb/IIIa. A theoretical study

F.D.SUVIRE; M MAK; J GY PAPP; ENRIZ R.D.

JOURNAL OF MOLECULAR STRUCTURE THEOCHEM

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2001 vol. 540 p. 271 - 283

0166-1280

In order to better understand, at a sub-molecular level, the minimal structural requirements for the recognition process in the platelet aggregation inhibitory activity, a series of RGD mimetics were examined as ®brinogen receptor antagonists variants. We simulate the electronic interactions between RGD with its biological receptor in terms of smaller molecules. MeCOO2 was used to mimic the side chain of deprotonated Asp and Meguanidinium group mimicked the side chain of the protonated Arg. Alternative moieties present on the RGD mimetics were also studied in this report. AM1; RHF/3-21G; B3LYP/6-3111Gpp in the gas phase. Also, B3LYP/6-3111Gpp calculations using the IPCM solvation model were carried out for all the complexes. Our results indicate that high level of theory calculations and the inclusion of solvent effects are crucial in order to obtain satisfactory of accuracy in the electronic distributions of these compounds.