Microwave-assisted solid-phase synthesis, cellular uptake, and cytotoxicity studies of cymantrene–peptide bioconjugates

Five cymantrene (CpMn(CO)3) bioconjugates of enkephalin (ENK), neurotensin (NT), pseudoneurotensin (pNT), NLS, and TAT were prepared by automated solid phase peptide synthesis (SPPS) under microwave irradiation in all steps, including peptide chain elongation, incorporation of the cymantrene moiety, final deprotection, and cleavage from the resin. The compounds were obtained in pure form with minimal work-up procedures and characterized by RP-HPLC, ESI-MS, and IR spectroscopy. They are efficiently internalized in HT-29 human colon cancer cells (0.22 to 0.48 nmol Mn/mg cell protein) and non-cytotoxic at up to 100 μM. With the carbonyl CO bands clearly detectable even in the presence of an octapeptide chain as in the cymantrene–NLS conjugate, these compounds will be useful as IR spectroscopic probes in peptide biodistribution studies.

Cymantrene is a robust organometallic biomarker which can be introduced to peptides using a fully automated solid-phase synthesis protocol under microwave irradiation in all steps to give bioconjugates in good yield and purity.Figure optionsDownload as PowerPoint slide