title: Synthesis of Mono-PEGylated Growth Hormone Releasing Peptide-2 and Investigation of its Biological Activity.
abstract: The purpose of this study was to investigate an efficient synthetic route to the mono-PEGylated growth hormone releasing peptide-2 (GHRP-2) and its biological activity in vivo. The commercially available key PEGylating reagent, mPEG-NHS ester, was successfully utilized to the synthesis of mono-PEGylated GHRP-2, during which the PEGylation profiles of GHRP-2 were monitored by high-performance liquid chromatography (HPLC). The product was purified by cation exchange chromatography, and its biological activity was conducted in rats. The desired mono-PEGylated GHRP-2 as the major product was readily obtained in anhydrous aprotic solvent, such as dimethyl formamide (DMF) and dimethylsulfoxide (DMSO), when the molar ratio of mPEG-NHS ester to GHRP-2 was fixed to be 0.8:1. The products were characterized by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry. The evaluation of the biological activity for the products showed that the mono-PEGylated GHRP-2 gave a more stable activity than GHRP-2, suggesting that PEGylation led to the increase in the half-life of GHRP-2 in plasma without greatly impairing the biological activity. PEGylation of the GHRP-2 is a good choice for the development of the GHRP-2 applications.
authors.affiliation: Department of Pharmacy, Zhejiang Pharmaceutical College, No. 888, Yinxian Avenue, Ningbo, 315100, People's Republic of China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Pharmacy, Zhejiang Pharmaceutical College, No. 888, Yinxian Avenue, Ningbo, 315100, People's Republic of China. xvbeihua@163.com.
authors.forename: Beihua
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Pharmacy, Zhejiang Pharmaceutical College, No. 888, Yinxian Avenue, Ningbo, 315100, People's Republic of China.
authors.forename: Ziniu
authors.initials: Z
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002021:Buffers; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D004126:Dimethylformamide / Q000737:chemistry; D004339:Drug Compounding; D004355:Drug Stability; D005260:Female; D013006:Growth Hormone / Q000097:blood; D006207:Half-Life; D007275:Injections, Intravenous; D009842:Oligopeptides / Q000008:administration & dosage* / Q000097:blood / Q000138:chemical synthesis / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000138:chemical synthesis*; D017207:Rats, Sprague-Dawley; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D002021:Buffers; D009842:Oligopeptides; D012997:Solvents; D011092:Polyethylene Glycols; D004126:Dimethylformamide; D013006:Growth Hormone; C028210:monomethoxypolyethylene glycol; C091874:growth hormone-releasing peptide-2; D004121:Dimethyl Sulfoxide
keywords: PEGylation; growth hormone; growth hormone releasing peptide-2; mPEG-NHS; mono-PEGylated GHRP-2