Phenyl-, Cyclohexyl- and BCP-Amino Acids

Phenyl-, Cyclohexyl- and BCP-Amino Acids

Published on 13/05/2020

Sidechain-derivatized amino acids have shown great potential in enhancing select properties of peptide lead compounds. Find the most recent additions to our portfolio of amino acids bearing additional aryl and alkyl groups in their side chains.

Adding a phenyl group to the side chain of any amino acid in a given peptide sequence may lead to improved binding properties of the peptide. One example of such a case is the antiviral drug Nelfinavir (Viracept®) which inhibits HIV-1 and HIV-2 proteases. A key structural element of Nelfinavir for optimal binding to HIV protease is an S-phenyl cysteine moiety as a substituent in position P1 (G. Klebe; Pharmazie in unserer Zeit 2001). Interestingly, Nelfinavir has also been shown to strongly inhibit the replication of SARS coronavirus (SARS-CoV) and is currently being tested as a potential treatment for COVID-19 (Yamamoto et al.; Biochem Biophys Res Commun 2004).


In case a lower aromatic ring count is desirable, the phenyl group can be replaced by the bioisostere bicyclo[1.1.1]pentane (BCP) motif. Accordingly derivatized amino acids are now also available from Iris Biotech.

Cyclohexyl groups were introduced as sidechain protecting groups by the Merrifield lab in the early days of peptide chemistry, but soon went out of fashion due to the harsh deprotection conditions required (HF). Similar to phenyl groups, however, cyclohexyl moieties may also be employed to optimize binding of promising lead structures, e.g. leading to much lower IC50 values of a peptide inhibitor against Hepatitic C Virus NS3/4A protease (Nizi et al.; Bioorg Med Chem Lett 2004).

cyclohexyl- and bcp-aas

→In case you don’t find your desired derivative in our portfolio, send your inquiry to our Custom Synthesis Service!


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