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Growth Factors. 2015 Apr;33(2):160-8. doi: 10.3109/08977194.2015.1010644. Epub 2015 Mar 23.

Synthesis and biological evaluation of novel structure-related hGHRH agonistic analogs.

Author information

1
Department of Biochemistry and Molecular Biology, School of Basic Courses, Guangdong Pharmaceutical University , Guangzhou , China .

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.

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

PMID:
25798996
DOI:
10.3109/08977194.2015.1010644
[Indexed for MEDLINE]

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