Monoclonal antibodies peptidomimetic

Novel inhibitors of glycoprotein Ilb/IIIa and fibrinogen/van WiUebrand interaction include injectable peptides (e.g. integrilin, 175) and orally active peptidomimetics that act as competitive inhibitors and a monoclonal antibody c7E3 (abciximab) that irreversibly binds to GP Ilb/ Ilia. 

Integrin ayPs, the vitronectin receptor, has been identi-hed as a promising potential target for the treatment of osteoporosis, diabetic retinopathy and cancer. Three classes of integrin antagonists are currently in preclinical and clinical development monoclonal antibodies targeting the extracellular domain of the heterodimer, vitaxin, synthetic peptides such as cilengitide and several peptidomimetics. ... 

For their preparation it is necessary, as a first step, to synthesize Boc-protected a-aza-amino acid monomers. Liquid-phase procedures have been optimized for the synthesis of a MeO-PEG-supported Leu-enkephalin azatide (YaGaG FaLa) analogue [90], Unfortunately, this peptidomimetic does not compete with the natural peptide in an ELISA for a specific monoclonal antibody. This was not completely unexpected by the authors because azatide adopts an extended conformation within the critical glycine region, while the bioactive peptide conformation is thought to be a sort of (3-turn. Starting from N-pro-tected a-aza amino acid residues, the generation of combinatorial azatide libraries seems to be feasible. 

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