title: A novel method for the large-scale production of PG-CNP37, a C-type natriuretic peptide analogue.
abstract: Achondroplasia is the most common form of human dwarfism caused by a mutation in the fibroblast growth factor receptor 3 (FGFR3), resulting in abnormal endochondral bone formation. C-type natriuretic peptide (CNP) is a potent stimulator of endochondral bone growth and represents a potential therapy for achondroplasia. We have developed a novel, simple and cost effective method to produce a CNP analogue, PG-CNP37, at a large scale from Escherichia coli. A PG-CNP37 fusion protein was over-expressed as inclusion bodies in E. coli, which were purified then cleaved by formic acid to release the PG-CNP37 peptide. Approximately 0.5g of 95% pure, soluble and active PG-CNP37 peptide was produced from 1L of culture using this method and may represent a viable means for large-scale production of other therapeutic peptides.
authors.affiliation: BioMarin Pharmaceutical, Inc., Novato, CA 94949, USA. slong@bmrn.com
authors.forename: Shinong
authors.initials: S
authors.lastname: Long
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Wendt
authors.forename: Sean M
authors.initials: SM
authors.lastname: Bell
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Taylor
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Dewavrin
authors.forename: Michel C
authors.initials: MC
authors.lastname: Vellard
mesh_terms: D002852:Chromatography, Ion Exchange; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000378:metabolism; D005561:Formates; D002479:Inclusion Bodies / Q000378:metabolism; D020098:Natriuretic Peptide, C-Type / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D005561:Formates; D011993:Recombinant Fusion Proteins; C030544:formic acid; D020098:Natriuretic Peptide, C-Type