AbstractAlternative RGD mimetics—with the exception of glycine—c(Arg‐Asp)1, c(Arg‐Glu)2and c[Arg‐Asp(Phe‐OH)]3were synthesized. The DKPs were prepared on solid phase with orthogonal protection allowing further derivatization in solution. During solution phase cyclization in NH3/methanol, the side chain benzyl ester group of H‐Arg(Tos)‐Asp(OBzl)‐OMe and H‐Arg(Tos)‐Glu(OBzl)‐OMe suffer transesterification, while β‐t‐butyl or β‐cyclohexyl esters are stable under the same conditions. In spite of the simple structure, all compounds bind selectively to the αvβ3integrin receptor,3showing the highest affinity with an IC50value of 0.74 µMvalue. On the other hand only3binds with measurable activity to the αIIbβ3receptor (IC50159 µM). The binding affinities seem to be in accordance with the distances between the arginine guanidino and the aspartic acid carboxyl group in extended conformation determined by semiempirical geometry optimization. Copyright © 2006 European Pe