10 November 2016:
In this latest review paper, CNBP researchers Xiaozhou (Michelle) Zhang (pictured left) and Prof Andrew Abell explore the preparation and properties of peptide-based macrocycles that target important therapeutic aims for conditions such as cancer, cataract, HIV, and neurological diseases.
Journal: Australian Journal of Chemistry.
Title: Macrocyclic Peptidomimetics Prepared by Ring-Closing Metathesis and Azide-Alkyne Cycloaddition.
Authors: Ashok D Pehere, Xiaozhou Zyhang and Andrew D Abell.
Abstract: Macrocycles are finding increasing use as a means to define the backbone geometries of peptides and peptidomimetics.Ring-closing metathesis and CuI-catalyzed azide–alkyne cycloaddition are particularly useful for introducing such rings and they do so in high yield and with a good functional group tolerance and compatibility. Here, we present an overview of the use of these two methods, with reference to selected examples and particular reference to b-strand peptidomimetics for use as protease inhibitors.
The paper is accessible online.
13 September 2016:
CNBP researchers Xiaozhou (Michelle) Zhang & Prof Andrew Abell explore peptidomimetic boronates as proteasome inhibitors in the latest issue of ACS Medicinal Chemistry Letters.
Journal: ACS Medicinal Chemistry Letters.
Title: New Peptidomimetic Boronates for Selective Inhibition of the Chymotrypsin-Like Activity of the 26S Proteasome.
Authors: Xiaozhou Zhang, Alaknanda Adwal, Andrew G Turner, David F Callen and Andrew D Abell.
Abstract: Proteasome is a large proteinase complex that degrades proteins via its three catalytic activities. Among these activities, the ‘chymotrypsin-like’ activity has emerged as the focus of drug discovery in cancer therapy. Here, we report new peptidomimetic boronates that are highly specific for the chymotrypsin-like catalytic activity of the proteasome. These new specific proteasome inhibitors demonstrated higher in vitro potency and selective cytotoxicity for cancer cells compared to benchmark proteasome inhibitors, bortezomib and carfilzomib. In breast cancer cell lines, treatment with 1a or
2a induced accumulation of the high molecular weight polyubiqutinated proteins at similar levels observed for borte-zomib and carfilzomib, indicating that cancer cell death caused by 1a/2a is chiefly due to proteasome inhibition.
The paper can be accessed online.
23 June 2016:
CNBP researchers Xiaozhou (Michelle) Zhang (pictured left) and Prof Andrew Abell (CNBP Chief Investigator) report on an NMR and X-ray crystallography-based characterisation of the mechanism by which a new class of macrocyclic peptidomimetic aldehyde inhibits α-chymotrypsin.
This provides molecular level insight into the mechanism and functionalities of proteases, which are crucial for many biological systems including neuronal, embryonic and cardiovascular systems.
Journal: Organic & Biomolecular Chemistry
Publication title: A mechanistic study on the inhibition of α-chymotrypsin by a macrocyclic peptidomimetic aldehyde.
Authors: X. Zhang, J. B. Bruning, J. H. George and A. D. Abell
Abstract: Here we describe an NMR and X-ray crystallography-based characterisation of the mechanism by which a new class of macrocyclic peptidomimetic aldehyde inhibits α-chymotrypsin. In particular, a 13C-labelled analogue of the inhibitor was prepared and used in NMR experiments to confirm formation of a hemiacetal intermediate on binding with α-chymotrypsin. Analysis of an X-ray crystallographic structure in complex with α-chymotrypsin reveals that the backbone adopts a stable β-strand conformation as per its design. Binding is further stabilised by interaction with the oxyanion hole near the S1 subsite and multiple hydrogen bonds.
The paper is accessible online.
29 January 2016:
CNBP researchers featured prominently in the recent ‘Institute for Photonics and Advanced Sensing (IPAS) Best Papers’ competition.
The awards, presented in January 2016, aim to showcase the quality and impact of the research being conducted by IPAS members.
Winners for the best ECR led Paper were Abel Santos, Agnieszka Zuber and CNBP Research Fellow Xiaozhou (Michelle) Zhang.
The best PhD Student Led Paper Awards went to CNBP student Malcolm Purdey, Parul Mittal and Tess Reynolds.
The Best Transdisciplinary Paper with a Strong Medical/Animal Science Element went to CNBP senior researcher Melanie McDowall.
Full details on the awards, all of the winners and their papers can be found at the IPAS web site.