Structure and function relationships of three novel hGHRH-GGC analogs.
Growth hormone releasing hormone (GHRH) is one of the hypothalamus hormones. For its potential applications in agriculture and medicine, GHRH analog with higher activity and longer half-life has been looked for. By using the fusion expression with unique acid labile linker Asp-Pro and biochemical purification, the three novel GHRH peptides, Pro-Pro-hGHRH(1-44)-Gly-Gly-Cys, Pro-hGHRH(1-44)-Gly-Gly-Cys, and (1)Pro-GHRH(2-44)-Gly-Gly-Cys, were obtained. The peptide molecular weight with 5,455, 5,373 or 5,210 Da measured by EIS-MS is coincident with the actual values. The peptides at 0.1-10 microg/ml increased rat pituitary GH releases in a dose-dependent manner and at 5 microg/ml increased human pituitary GH releases. The activity comparisons showed that at 10 microg/ml there were significant between (1)Pro-hGHRH(2-44)-Gly-Gly-Cys and Pro-Pro-hGHRH(1-44)-Gly-Gly-Cys or Pro-hGHRH(1-44)-Gly-Gly-Cys, (1)Pro-hGHRH(2-44) (P<0.05). The (1)Pro-hGHRH(2-44)-Gly-Gly-Cys showed the highest GH release from rat pituitary. The activity results showed that the N-terminal Pro modulations and the C-terminal Gly-Gly-Cys extension regulate GH release from pituitary. The results showed that the three peptides had good GH release, function-selectivity and species specificity.
Tang
Song-Shan
SS
Department of Biochemistry & Molecular biology, School of Basic Courses, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Du
Ming-Hua
MH
Zhang
Juan-Hui
JH
Kong
Xin
X
Liu
Jing-Jing
JJ
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D015870:Gene Expression; D013007:Growth Hormone-Releasing Hormone / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism*; D017433:Protein Structure, Secondary; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D013329:Structure-Activity Relationship; D046509:Tissue Culture Techniques
D011993:Recombinant Fusion Proteins; D019382:Human Growth Hormone; D013007:Growth Hormone-Releasing Hormone