Methoxinine – an alternative stable amino acid substitute for oxidation‐sensitive methionine in radiolabelled peptide conjugates

We report here the use of methoxinine (Mox), a non‐canonical amino acid that resembles more closely the electronic properties of Met in comparison to Nle. Specifically, we replaced Met15 by Mox15 and Nle15 in the binding sequence of a radiometal‐labelled human gastrin derivative [d‐Glu10]HG(10‐17), named MG11 (d‐Glu‐Ala‐Tyr‐Gly‐Trp‐Met‐Asp‐Phe‐NH2). A comparison of the physicochemical properties of 177Lu‐DOTA[X15]MG11 (X = Met, Nle, Mox) in vitro (cell internalization/externalization properties, receptor affinity (IC50), blood plasma stability and logD) showed that Mox indeed represents a suitable, oxidation‐stable amino acid substitute of Met in radiolabelled peptide conjugates. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd. Replacement of the amino acid methionine by norleucine (X = CH2) and/or methoxinine (X = O) in the sequence of a minigastrin derivative provides tumour‐targeting peptide conjugates, which exhibit maintained biological activity and are stable towards oxidative side reactions during radiolabelling procedures.
Source: Journal of Peptide Science - Category: Biochemistry Authors: Tags: Research Article Source Type: research