Convenient solid-phase synthesis of Tyr3-octreotide

We have developed a new method to anchor Thr(ol) to a solid-phase synthesis resin for preparation of Tyr3-octreotide. Fmoc-Thr(ol)-terephthal-acetal, prepared from Fmoc-Thr-OH, was loaded onto the resin. After construction of the peptide chains by Fmoc chemistry, cyclization of the peptide may be obtained on-resin by oxidation with iodine in DMF. The cleavage of the peptide-resin with trifluoroacetic acid, followed by the reverse-phase HPLC purification, produced Tyr3-octreotide with an overall yield of 40% from the starting Fmoc-Thr(ol)-terephthal-acetal-resin. The final product gave a single peak on analytical HPLC and electrospray mass spectrometry confirmed the integrity of the product. Iodine-123 radiolabeling of the product provided 123I-Tyr3-octreotide with >98% radiochemical purity