A comparative examination of two Fmoc removal reagents for process improvement to produce peptide drugs

The importance of peptides as therapeutics has been recognized since they were found responsible for a wide variety of biological functions. The recent approval of peptide drugs such as Byetta (Amylin Pharmaceuticals, Inc.), Fuzeon (Hoffman-LaRoche Inc.), Integrelin (CDR Therapeutics, Inc.), Natrecor (SCIOS Inc.), Symlin (Amylin), Teriparatide, and Ziconotide, etc., which demonstrated applications for treatment of such problems as bone metabolism disorders, cardiovascular diseases, diabetes, viral infections and severe chronic pain control, has further endorsed the growing interest in peptides as a potential drug. This growing trend for peptide drugs has drawn our attention for their production in a cost-effective manner. To do so, the improvement in the quality of crude peptides during synthesis, the most critical parameter in the process, is important to prevent yield losses during the more expensive purification step. To accomplish it, we decided to examine the efficacy of the commonly used nucleophilic base piperidine and non-neucleophilic base DBU (1,8-Diazabicyclo[5.4.0]undec-7-ene) for the complete removal of Fmoc group during the synthesis of peptides. According to our investigation, application of piperidine was found more effective than DBU in solid phase synthesis. Details of the investigation will be discussed.