Cyclopropane Pipecolic Acids as Templates for Linear and Cyclic Peptidomimetics: Application in the Synthesis of an Arg‐Gly‐Asp (RGD)‐Containing Peptide as an αvβ3 Integrin Ligand. Issue 35 (28th July 2014)

• Record Type: Journal Article
• Authors: Sernissi, Lorenzo; Petrović, Martina; Scarpi, Dina; Guarna, Antonio; Trabocchi, Andrea; Bianchini, Francesca; Occhiato, Ernesto G.
• Is Part Of: Chemistry. Volume 20:Issue 35(2014)
• Page Start: 11187
• Page End: 11203
• Publication Date: 2014-07-28
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201403077
• Languages: English
• ISSNs: 0947-6539

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>The synthesis and evaluation of substituted cyclopropane pipecolic acids (CPA) as conformationally restricted templates for linear and cyclic peptidomimetics is reported. A variety of differently substituted (poly)hydroxy‐ and amino‐2‐azabicyclo[4.1.0]heptane‐1‐carboxylic acids were prepared by means of the Pd‐catalyzed methoxycarbonylation of suitably functionalized lactam‐derived enol phosphates, followed by OH‐directed cyclopropanation. CPAs were successfully introduced into a linear peptide sequence to assess the <italic>cis</italic>/<italic>trans</italic> isomerism about the pipecolic acid peptide bond, and in a cyclic peptidomimetic that bore the Arg‐Gly‐Asp (RGD) sequence, which displayed nanomolar activity as antagonist of the α_vβ₃ integrin in M21 human melanoma cells. Thus, CPAs appear to be suitable for the generation of novel peptidomimetics for drug discovery.</p> </abstract>