title: Synthesis and biological evaluation of novel structure-related hGHRH agonistic analogs.
abstract: Activity and half-life play key roles in the application of GHRH analogues. The GHRH monomers produced in a solid synthesizer were incubated, respectively, in NH4OH solution and lyophilized to obtain their dimers. The activities, specificities, and receptor affinities of the GHRH dimers were evaluated in rGH release/inhibition, rACTH/LH/PRL release, pituitary homogenate binding, and fluorescent staining. Compared to hGHRH(1-44)NH2 (S), PP-hGHRH(1-44)-GGC-CGG-hGHRH(44-1)-PP (2D), P-hGHRH(1-44)-GGC-CGG-hGHRH(44-1)-P (2E), (1)P-hGHRH(2-44)-GGC-CGG-hGHRH(44-2)-(1)P (2F), or hGHRH(1-44)-GGC-CGG-hGHRH(44-1) (2Y) had potency of 104 ± 16.7%, 94 ± 32.6%, 114 ± 16.6%, or 122 ± 14.5% and similar specificities. The inhibition effect of GHIH on rGH stimulated by GHRH dimer was in dose-/time-dependent manner. The staining of FITC-labeled dimer showed cytomembrane distribution and the binding ranking was 2F>2D>2Y>2E>S. 2F presents the strongest activity and the highest affinity to pituitary cells. The dimer with (1)Pro-GHRH stimulates stronger rGH release than that with (1)Tyr-GHRH and the N-terminal single cyclic amino acid is required for the stimulation.
authors: Department of Biochemistry and Molecular Biology, School of Basic Courses, Guangdong Pharmaceutical University , Guangzhou , China .
authors: Dong
authors: D
authors: Zhou
authors: Juan
authors: J
authors: You
authors: Qiu-Ying
authors: QY
authors: Li
authors: Hong-Zhi
authors: HZ
authors: Li
authors: Wen-Feng
authors: WF
authors: Wu
authors: Xu-Dong
authors: XD
authors: Zhang
authors: Juan-Hui
authors: JH
authors: Zhang
authors: Song-Shan
authors: SS
authors: Tang
authors: Yun-Ke
authors: YK
authors: Wang
authors: Tao
authors: T
authors: Liu
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry; D013006:Growth Hormone / Q000378:metabolism; D013007:Growth Hormone-Releasing Hormone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry*; D006728:Hormones / Q000378:metabolism; D006801:Humans; D008024:Ligands; D010446:Peptide Fragments / Q000737:chemistry; D010902:Pituitary Gland / Q000378:metabolism; D011485:Protein Binding; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000737:chemistry
chemical_list: D005456:Fluorescent Dyes; D006728:Hormones; D008024:Ligands; D010446:Peptide Fragments; D011994:Recombinant Proteins; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone
keywords: (H)1P-hGHRH(2–44)-GGC(OH)-(OH)CGG-hGHRH(44-2)-P1(H); (H)P-hGHRH(1–44)-GGC(OH)-(OH)C-GG-hGHRH(44-1)-P(H); (H)PP-hGHRH(1–44)-GGC(OH)-(OH)CGG-hGHRH(44-1)-PP(H); (H)hGHRH(1–44)-GGC(OH)-(OH)CGG-hGHRH(44-1)(H); Human growth hormone-releasing hormone analogue; structure–function relationship