Rapid and high-yield solution-phase synthesis of DOTA-Tyr3-octreotide and DOTA-Tyr3-octreotate using unprotected DOTA

✍ Scribed by Margret Schottelius; Markus Schwaiger; Hans-Jürgen Wester

• Book ID: 104253136
• Publisher: Elsevier Science
• Year: 2003
• Tongue: French
• Weight: 404 KB
• Volume: 44
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(03)00221-1

✦ Synopsis

An improved method for the solution-phase derivatization of Tyr 3 -Lys 5 (Dde)-octreotide (TOC(Dde)) and Tyr 3 -Lys 5 (Dde)-octreotate (TATE(Dde)) with the macrocyclic chelator DOTA (1,4,7,10-tetraazacyclododecane-N%,N¦,N §,N¨-tetraacetic acid) has been developed. The fully protected parent peptides were assembled via solid-phase peptide synthesis (SPPS) using Fmoc-strategy. After cleavage from the solid support, disulfide bond formation was carried out using H 2 O 2 . Both TOC(Dde) and TATE(Dde) were successfully coupled with DOTA in the presence of NHS, EDCI and DIPEA in a water/DMF solvent system. Yields of the coupling reaction were >98% within only 2 h with no detectable formation of sideproducts. This method for the preparation of DOTATOC, DOTATATE and other DOTA-peptide conjugates is therefore a rapid and economic alternative to the currently used methods.