Herein we have reported a novel strategy that leverages in situ generated TAD peptides (int-16) to achieve Tyrselective peptide cyclizations. The requisite urazole-containing peptides (14) are selectively oxidized under mild conditions to generate the reactive TAD-peptide intermediates, which are qualitatively characterized by the carmine color characteristic of the TAD chromophore. Upon dilution of the TAD-peptide intermediates using buffered aqueous conditions, cyclization occurs rapidly, and the crude reaction mixture is easily purified to give cyclic peptides (16) in good yield. This approach is tolerant of most native residue side chain functionalities and permits access to cyclic peptides that are 3-to 11residues in size, including lariat-type peptides. Ongoing developments, including the application of electrochemical oxidation protocols should expand residue tolerance to permit the ready incorporation of native Cys, Met, and Trp residues. The application of this method for generating bioactive Tyr-linked cyclic peptides was shown by the formation and evaluation of RGDf epitope-containing Tyr-linked cyclic peptides, 16y and 16z, that display adhesion inhibition properties similar to that of cilengitide as determined by separate cell adhesion assays using HUVECs and MCF-7 cells. This result demonstrates the potential application of this chemistry for developing therapeutic peptides and, alongside the procedural simplicity, should render this cyclization strategy as an attractive approach for chemists constructing novel therapeutic peptidomimetic leads.