An Alkyne-functionalized Arginine for Solid-Phase Synthesis Enabling “Bioorthogonal” Peptide Conjugation

Lately,
amino-functionalized Nω-carbamoylated
arginines were introduced as arginine surrogates enabling
peptide labeling. However, this approach is hardly compatible with
peptides also containing lysine or cysteine. Here, we present the
synthesis of an alkyne-functionalized, Nω-carbamoylated arginine building block (7), which is
compatible with Fmoc-strategy solid-phase peptide synthesis. The alkynylated
arginine was incorporated into three biologically active linear hexapeptides
and into a cyclic pentapeptide. Peptide conjugation to an azido-functionalized
fluorescent dye via “click” chemistry was successfully
demonstrated. In the case of a peptide also containing lysine besides
the alkyne-functionalized arginine, this was feasible in a “bioorthogonal”
manner.