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

Show simple item record Kowalczyk, Renata en Yang, Sung Hyun en Brimble, Margaret en Callon, Karen en Watson, Maureen en Park, Young Eun en Cornish, Jillian en 2016-10-07T03:37:39Z en 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 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 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 en
dc.rights.uri 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 en
pubs.end-page 3572 en
pubs.publication-status Published en
dc.rights.accessrights en
pubs.subtype Article en
pubs.elements-id 440823 en Academic Services en Examinations en Medical and Health Sciences en School of Medicine en Medicine Department en Ophthalmology Department en Science en Chemistry en Science Research en 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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