Synthesis of a macrocycle based on Linked Amino Acid Mimetics (LAAM)

We report the synthesis of a macrocycle utilizing a novel framework of standard amino acids in combination with subunits that we have named as Linked Amino Acid Mimetics (LAAMs). Macrocycles based on the LAAM concept provide both a peptide targeting region and two independently variable functional regions. In the prototype structure, the commonly known Arg-Gly-Asp (RGD) sequence was used for the targeting region. The functional regions contain a phenyl group, and the linkage was formed via a Ring-Closing Metathesis (RCM) reaction. We report the synthesis of a macrocycle utilizing a novel framework of standard amino acids in combination with subunits that we have named as Linked Amino Acid Mimetics (LAAMs). Macrocycles based on the LAAM concept provide both a peptide targeting region and two independently variable functional regions. In the prototype structure, the commonly known Arg-Gly-Asp (RGD) sequence was used for the targeting region. The functional regions contain a phenyl group, and the linkage was formed via a Ring-Closing Metathesis (RCM) reaction.