Stereodivergent synthesis of 5-aminopipecolic acids and application in the preparation of a cyclic RGD peptidomimetic as a nanomolar αVβ3 integrin ligand

Literature Information

Publication Date 2018-04-11
DOI 10.1039/C8OB00534F
Impact Factor 3.876
Authors

Lorenzo Sernissi, Luciano Ricci, Dina Scarpi, Francesca Bianchini, Daniela Arosio, Alessandro Contini, Ernesto G. Occhiato


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Abstract

A stereodivergent strategy was devised to obtain enantiopure cis and trans 5-aminopipecolic acids (5-APAs) in suitably protected forms to be employed in peptide synthesis as conformationally constrained α- and δ-amino acids. The cis isomer was used as a δ-amino acid to construct a cyclic RGD-containing peptidomimetic, the ability of which to compete with biotinylated vitronectin for binding with the isolated αVβ3 integrin was measured (IC50 = 4.2 ± 0.9 nM). A complete 1H NMR and computational conformational analysis was performed to elucidate the reasons for the high affinity of this cyclic peptidomimetic in comparison with cilengitide.

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Organic & Biomolecular Chemistry

Organic & Biomolecular Chemistry
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Organic & Biomolecular Chemistry (OBC) publishes original and high impact research and reviews in organic chemistry. We welcome research that shows new or significantly improved protocols or methodologies in total synthesis, synthetic methodology or physical and theoretical organic chemistry as well as research that shows a significant advance in the organic chemistry or molecular design aspects of chemical biology, catalysis, supramolecular and macromolecular chemistry, theoretical chemistry, mechanism-oriented physical organic chemistry, medicinal chemistry or natural products. Articles published in the journal should report new work which makes a highly-significant impact in the field. Routine and incremental work is generally not suitable for publication in the journal. More details about key areas of our scope are below. In all cases authors should include in their article clear rationale for why their research has been carried out.

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