A Solid-Phase Synthetic Strategy for Labeled Peptides: Synthesis of a Biotinylated Derivative of the δ Opioid Receptor Antagonist TIPP (Tyr-Tic-Phe-Phe-OH)

Abstract

A general solid-phase synthetic strategy for labeled peptides was developed and used to prepare a biotinylated derivative of the delta opioid receptor antagonist TIPP (Tyr-Tic-Phe-Phe-OH). A monoprotected hydrophilic diamine linker was attached to an aldehyde-containing solid-phase resin by reductive amination, followed by introduction of biotin and peptide synthesis to yield Tyr-Tic-Phe-Phe-Asp-NH(CH(2)CH(2)O)(2)CH(2)CH(2)NH-biotin (2). The high delta receptor affinity and selectivity of 2 demonstrate the applicability of this design approach for labeled peptide derivatives.