An optimized strategy for the mild and efficient solution phase iodination of tyrosine residues in bioactive peptides

Usually, the accessibility of 3-iodo-Tyr-containing peptides relies on the time-consuming de novo solid phase peptide synthesis. In this study, methods for the direct (mono)iodination of unprotected peptides were evaluated. The use of N-iodosuccinimide (NIS) in acetonitrile/water proved to be a particularly mild, fast (≤5 min) and efficient method with broad applicability to structurally diverse peptides. NIS iodination therefore represents a very practicable tool for the generation of iodinated peptides on a small (<1 mg) to medium (1-20 mg) scale in reasonable isolated yields (28 ± 8%), providing easy and straightforward access to iodinated reference compounds, for example, for in vitro evaluation.