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Synthesis of a Chloroalkene Dipeptide Isostere-Containing Peptidomimetic and Its Biological Application.

ABSTRACT: The first rapid and efficient chemical synthesis of a cyclic Arg-Gly-Asp (RGD) peptide containing a chloroalkene dipeptide isostere (CADI) is reported. By a developed synthetic method, an N-tert-butylsulfonyl protected CADI was obtained utilizing diastereoselective allylic alkylation as a key reaction. This CADI was also transformed into an N-Fmoc protected CADI in a few steps. The CADI was used in Fmoc-based solid-phase peptide synthesis. The first synthesis of a CADI-containing cyclic RGD peptide was successful, and the synthesized CADI-containing peptidomimetic was found to be a more potent inhibitor against integrin-mediated cell attachment than the parent cyclic peptide.

SUBMITTER: Kobayakawa T

PROVIDER: S-EPMC5767888 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Synthesis of a Chloroalkene Dipeptide Isostere-Containing Peptidomimetic and Its Biological Application.

Kobayakawa Takuya T Matsuzaki Yudai Y Hozumi Kentaro K Nomura Wataru W Nomizu Motoyoshi M Tamamura Hirokazu H

ACS medicinal chemistry letters 20171227 1

The first rapid and efficient chemical synthesis of a cyclic Arg-Gly-Asp (RGD) peptide containing a chloroalkene dipeptide isostere (CADI) is reported. By a developed synthetic method, an N-tert-butylsulfonyl protected CADI was obtained utilizing diastereoselective allylic alkylation as a key reaction. This CADI was also transformed into an N-Fmoc protected CADI in a few steps. The CADI was used in Fmoc-based solid-phase peptide synthesis. The first synthesis of a CADI-conta ...[more]

PMID: 29348803

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