Study on preparation and activity of a novel recombinant human parathyroid hormone(1–34) analog with N-terminal Pro–Pro extension

Wang, Chunxiao; Liu, Jingjing; Yire, Xiao; Dai, Min; Wang, Zhaohui; Qi, Gaofu; Shen, Xiangchun; Wang, Xuejun; Wu, Jie; Li, Taiming

doi:10.1016/j.regpep.2006.12.020

Cited by 14 publications

(7 citation statements)

References 21 publications

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“…The distinct morphology of PTH‐loaded coatings suggests that PTH has entered the lattice structure of the CaP coating and bonded with the mineral. The isoelectric point (pKa) of PTH 1–34 is 8.0, so the PTH molecule should have been positively charged under the pH of m‐SBF (6.5–7.0) 55. As a result, it is possible that there is an interaction between the negatively charged phosphate groups of the CaP coating and the PTH molecules.…”

Section: Discussionmentioning

confidence: 99%

Preparation and evaluation of parathyroid hormone incorporated CaP coating via a biomimetic method

Wei

2011

J Biomed Mater Res

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Parathyroid hormone (PTH) is a potent bone growth stimulator used for osteoporosis treatment. However, the inconvenience of daily administration and side effect of systemic exposure severely limit its use in clinical applications. Local, controlled delivery is a promising approach which can maintain therapeutic concentration locally for a long period. In this study, PTH was incorporated into a biomimetic calcium phosphate (CaP) coating via a coprecipitation process in a modified simulated body fluid (m-SBF). It was found that PTH was successfully incorporated into biomimetic CaP coating on titanium surface with a high incorporation efficiency. The incorporation of PTH into coatings had significantly changed the coating morphology, but the composition of the coating remained unchanged. Localized release of PTH had occurred in vitro, and was accompanied with partial dissolution of CaP coatings. Cell culture study demonstrated that the PTH released from CaP coatings fully retained its bioactivity. It had improved substantially MC3T3-E1 cell proliferation but slightly delayed the expression of alkaline phosphatase (ALP) of the cells. In summary, our results have shown that CaP coatings incorporated with PTH may be a promising approach for osteoporosis and other bone-related disease treatment in the future.

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Section: Discussionmentioning

confidence: 99%

Preparation and evaluation of parathyroid hormone incorporated CaP coating via a biomimetic method

Wei

2011

J Biomed Mater Res

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“…Similarly, a tetra-substituted analog of GHRH (1–29) circumvents proteolytic cleavage by associating with serum albumin [74] . Introduction of two proline residues at the very N-terminus of PTH (1–34) generated an analog that is resistant against degradation by dipeptidase and that is currently in use for the treatment of osteoporosis [75] .…”

Section: Structure-based Chemical Modification Of Peptide Ligands Is mentioning

confidence: 99%

Structure and mechanism for recognition of peptide hormones by Class B G-protein-coupled receptors

2012

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Class B G-protein-coupled receptors (GPCRs) are receptors for peptide hormones that include glucagon, parathyroid hormone, and calcitonin. These receptors are involved in a wide spectrum of physiological activities, from metabolic regulation and stress control to development and maintenance of the skeletal system. As such, they are important drug targets for the treatment of diabetes, osteoporosis, and stress related disorders. Class B GPCRs are organized into two modular domains: an extracellular domain (ECD) and a helical bundle that contains seven transmembrane helices (TM domain). The ECD is responsible for the high affinity and specificity of hormone binding, and the TM domain is required for receptor activation and signal coupling to downstream G-proteins. Although the structure of the full-length receptor remains unknown, the ECD structures have been well characterized for a number of Class B GPCRs, revealing a common fold for ligand recognition. This review summarizes the general structural principles that guide hormone binding by Class B ECDs and their implications in the design of peptide hormone analogs for therapeutic purposes.

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“…The hPTH' improved the structure, composition and mechanical properties of bone in rats [74]. In OVX rats, daily s.c. injections of Pro-Pro-hPTH(1 --34) for 16 weeks resulted in significant BMD increases (17.5 --22.3%) compared to sham-operated groups [75]. Further, hPTH' led to significantly greater increments in BMD, trabecular width and bone formation markers than teriparatide [72].…”

Section: Zp2307 [Cyclic Pth (1 --17)]mentioning

confidence: 91%

Investigational parathyroid hormone receptor analogs for the treatment of osteoporosis

Polyzos

Makras

Efstathiadou

et al. 2014

Expert Opinion on Investigational Drugs

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β-arrestins are multifunctional cytoplasmic molecules that are decisive for regulating intracellular PTH signaling. Recently, in preclinical studies, arrestin analogs have achieved the anabolic bone effect of PTH without an accompanying increase in bone resorption. However, it is not yet known whether these analogs have adverse effects and there are no clinical data for their efficacy to date. On the other hand, several molecules derived either from PTH and PTH-related protein (PTHrP) molecules have been developed. Alternative routes of PTH 1 - 34 delivery (oral, transdermal), the PTH analog ostabolin and the N-terminal PTHrP analogs PTHrP 1 - 36 and abaloparatide, have recently been or are currently being tested in clinical trials and are more likely to become available for use in the near future.

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Study on preparation and activity of a novel recombinant human parathyroid hormone(1–34) analog with N-terminal Pro–Pro extension

Cited by 14 publications

References 21 publications

Preparation and evaluation of parathyroid hormone incorporated CaP coating via a biomimetic method

Preparation and evaluation of parathyroid hormone incorporated CaP coating via a biomimetic method

Structure and mechanism for recognition of peptide hormones by Class B G-protein-coupled receptors

Investigational parathyroid hormone receptor analogs for the treatment of osteoporosis

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