Synthesis of truncated analogues of preptin-(1-16), and investigation of their ability to stimulate osteoblast proliferation

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dc.contributor.author Kowalczyk, Renata en
dc.contributor.author Yang, Sung Hyun en
dc.contributor.author Brimble, Margaret en
dc.contributor.author Callon, Karen en
dc.contributor.author Watson, Maureen en
dc.contributor.author Park, Young Eun en
dc.contributor.author Cornish, Jillian en
dc.date.accessioned 2016-10-07T03:37:39Z en
dc.date.issued 2014-07-15 en
dc.identifier.citation Bioorganic and Medicinal Chemistry, 2014, 22 (14), pp. 3565 - 3572 en
dc.identifier.issn 0968-0896 en
dc.identifier.uri http://hdl.handle.net/2292/30665 en
dc.description.abstract Preptin, a 34-amino acid residue peptide hormone is co-secreted with insulin from the β-pancreatic cells and is active in fuel metabolism. We have previously established that a shorter fragment of preptin, namely preptin-(1–16), stimulates bone growth by proliferation and increasing the survival rate of osteoblasts. This was demonstrated in both in vitro and in vivo models. These findings suggest that preptin-(1–16) could play an important role in the anabolic therapy of osteoporosis. However, due to the large size of the peptide it is not an ideal therapeutic agent. The aim of this study was to identify the shortest preptin analogue that retains or even increases the bone anabolic activity as compared to the parent preptin-(1–16) peptide. Truncations were made in a methodical manner from both the N-terminus and the C-terminus of the peptide, and the effect of these deletions on the resulting biological activity was assessed. In order to improve the enzymatic stability of the shortest yet active analogue identified, ruthenium-catalysed ring closing metathesis was used to generate a macrocyclic peptide using allylglycine residues as handles for ring formation. We have successfully identified a short 8-amino acid preptin (1–8) fragment that retains an anabolic effect on the proliferation of primary rat osteoblasts and enhances bone nodule formation. Preptin (1–8) is a useful lead compound for the development of orally active therapeutics for the treatment of osteoporosis. en
dc.description.uri http://www.journals.elsevier.com/bioorganic-and-medicinal-chemistry/ en
dc.publisher Elsevier en
dc.relation.ispartofseries Bioorganic and Medicinal Chemistry en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from http://www.sherpa.ac.uk/romeo/issn/0968-0896/ en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.title Synthesis of truncated analogues of preptin-(1-16), and investigation of their ability to stimulate osteoblast proliferation en
dc.type Journal Article en
dc.identifier.doi 10.1016/j.bmc.2014.05.026 en
pubs.issue 14 en
pubs.begin-page 3565 en
pubs.volume 22 en
dc.rights.holder Copyright: Elsevier en
dc.identifier.pmid 24932835 en
pubs.author-url http://www.sciencedirect.com/science/article/pii/S0968089614003757 en
pubs.end-page 3572 en
pubs.publication-status Published en
dc.rights.accessrights http://purl.org/eprint/accessRights/RestrictedAccess en
pubs.subtype Article en
pubs.elements-id 440823 en
pubs.org-id Academic Services en
pubs.org-id Examinations en
pubs.org-id Medical and Health Sciences en
pubs.org-id School of Medicine en
pubs.org-id Medicine Department en
pubs.org-id Ophthalmology Department en
pubs.org-id Science en
pubs.org-id Chemistry en
pubs.org-id Science Research en
pubs.org-id Maurice Wilkins Centre (2010-2014) en
dc.identifier.eissn 1464-3391 en
pubs.record-created-at-source-date 2016-10-07 en
pubs.dimensions-id 24932835 en


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