CONVENIENT SOLID-PHASE SYNTHESIS OF TYR(3)-OCTREOTIDE

We have developed a new method to anchor Thr(ol) to a solid-phase synt hesis resin for preparation of Tyr(3)-octreotide. Fmoc-Thr(ol)-terepht hal-acetal, prepared from Fmoc-Thr-OH, was loaded onto the resin. Afte r 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 Tyr(3)-octreotide wi th an overall yield of 40% from the starting Fmoc-Thr(ol)-terephthal-a cetal-resin. The final product gave a single peak on analytical HPLC a nd electrospray mass spectrometry confirmed the integrity of the produ ct. Iodine-123 radiolabeling of the product provided I-123-Tyr(3)-octr eotide with >98% radiochemical purity. (C) 1998 Published by Elsevier Science Ltd. All rights reserved.