dc.contributor.author |
Kowalczyk, R |
en |
dc.contributor.author |
Brimble, MA |
en |
dc.contributor.author |
Callon, Karen |
en |
dc.contributor.author |
Watson, Maureen |
en |
dc.contributor.author |
Cornish, J |
en |
dc.date.accessioned |
2016-10-05T04:29:58Z |
en |
dc.date.issued |
2012-10-15 |
en |
dc.identifier.citation |
Bioorganic and Medicinal Chemistry, 2012, 20 (20), pp. 6011 - 6018 |
en |
dc.identifier.issn |
0968-0896 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/30621 |
en |
dc.description.abstract |
When administered in vivo, amylin (1–8) stimulates osteoblast proliferation increasing bone volume and bone strength. The native cyclic octapeptide amylin (1–8) is unstable, however, it provides an attractive framework for the creation of more stable, orally active synthetic analogues using various peptidomimetic techniques. On-resin ring closing metathesis (RCM) on the olefinic side chains of allylglycine residues and lysine moieties functionalized with an allyloxycarbonyl (Alloc) group, was used to prepare novel carba-bridged surrogates of the disulfide bridge between Cys/2 and Cys/7 in amylin-(1–8). Commercially available Nα-Fmoc Nε-Alloc protected lysine was used as a convenient substrate for Grubbs’ ring closing metathesis. Analogues of amylin-(1–8) prepared by cyclization of allylglycine residues that also contained proline residues at either position 4 or 6, or both, were also prepared to investigate the effect of proline as a ‘kink-inducing’ residue on the efficiency of the RCM reaction. Of the nine novel alkene-bridged analogues prepared, five showed promising biological activity in a proliferation study in primary foetal rat osteoblasts at physiological concentrations. Two of these analogues were chosen for further in vivo evaluation. |
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 |
How to blast osteoblasts? Novel dicarba analogues of amylin-(1-8) to treat osteoporosis |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1016/j.bmc.2012.08.053 |
en |
pubs.issue |
20 |
en |
pubs.begin-page |
6011 |
en |
pubs.volume |
20 |
en |
dc.rights.holder |
Copyright: Elsevier |
en |
dc.identifier.pmid |
22998786 |
en |
pubs.author-url |
http://www.sciencedirect.com/science/article/pii/S0968089612006888 |
en |
pubs.end-page |
6018 |
en |
pubs.publication-status |
Published |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
361320 |
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 |
2012-12-17 |
en |
pubs.dimensions-id |
22998786 |
en |