CAS: 664334-36-5; Bl-8040

专利信息

专利号:US-11993631-B2
优先权日:2020-12-30
标题:Process for manufacturing peptide
发明人：HALBFINGER EFRAT
权利人:BIOLINERX LTD
摘要:A large-scale process is described herein for preparing a cyclic peptide as described, comprising solid phase peptide synthesis of a linear peptide and cleaving it from the resin; oxidizing cysteine residues to form an intramolecular disulfide bond; and isolating the cyclic peptide, wherein:(i) coupling uses diisopropylcarbodiimide and ethyl cyanohydroxyiminoacetate and/or N-hydroxybenzotriazole;(ii) cleaving comprises contacting the peptide with a solution comprising TFA and dithioerythritol and/or dithiothreitol;(iii) the peptide is precipitated after cleaving without prior concentration of the peptide by evaporation;(iv) oxidizing comprises contacting an aqueous solution comprising at least 5 mg/mL peptide with hydrogen peroxide;(v) isolating comprises loading the peptide on a reverse phase chromatography at up to 40 grams/kg column, and elution from the column;(vi) isolating comprises lyophilization, followed by grinding the peptide; and/or(vii) substitution of the resin is at least 0.3 milliequivalents/gram, and/or the resin is a Rink aminomethylstyrene resin.