ORCID Profile
0000-0003-0960-8197
Current Organisation
University of Adelaide
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Publisher: Wiley
Date: 20-10-2016
Publisher: Wiley
Date: 19-07-2018
Publisher: Wiley
Date: 24-08-2020
Publisher: Wiley
Date: 20-10-2016
Abstract: Despite recent advances in the treatment of diabetes mellitus, storage of insulin formulations at 4 °C is still necessary to minimize chemical degradation. This is problematic in tropical regions where reliable refrigeration is not ubiquitous. Some degradation byproducts are caused by disulfide shuffling of cystine that leads to covalently bonded oligomers. Consequently we examined the utility of the non‐reducible cystine isostere, cystathionine, within the A‐chain. Reported herein is an efficient method for forming this mimic using simple monomeric building blocks. The intra‐A‐chain cystathionine insulin analogue was obtained in good overall yield, chemically characterized and demonstrated to possess native binding affinity for the insulin receptor isoform B. It was also shown to possess significantly enhanced thermal stability indicating potential application to next‐generation insulin analogues.
Publisher: Wiley
Date: 19-07-2018
Abstract: The human sliding cl (PCNA) controls access to DNA for many proteins involved in DNA replication and repair. Proteins are recruited to the PCNA surface by means of a short, conserved peptide motif known as the PCNA-interacting protein box (PIP-box). Inhibitors of these essential protein-protein interactions may be useful as cancer therapeutics by disrupting DNA replication and repair in these highly proliferative cells. PIP-box peptide mimetics have been identified as a potentially rapid route to potent PCNA inhibitors. Here we describe the rational design and synthesis of the first PCNA peptidomimetic ligands, based on the high affinity PIP-box sequence from the natural PCNA inhibitor p21. These mimetics incorporate covalent i,i+4 side-chain/side-chain lactam linkages of different lengths, designed to constrain the peptides into the 3
Publisher: Wiley
Date: 23-07-2018
Publisher: Wiley
Date: 23-06-2021
Abstract: An i−i +4 or i−i +3 bimane‐containing linker was introduced into a peptide known to target Estrogen Receptor alpha (ERα), in order to stabilise an α‐helical geometry. These macrocycles were studied by CD and NMR to reveal the i−i +4 constrained peptide adopts a 3 10 ‐helical structure in solution, and an α‐helical conformation on interaction with the ERα coactivator recruitment surface in silico . An acyclic bimane‐modified peptide is also helical, when it includes a tryptophan or tyrosine residue but is significantly less helical with a phenylalanine or alanine residue, which indicates such a bimane modification influences peptide structure in a sequence dependent manner. The fluorescence intensity of the bimane appears influenced by peptide conformation, where helical peptides displayed a fluorescence increase when TFE was added to phosphate buffer, compared to a decrease for less helical peptides. This study presents the bimane as a useful modification to influence peptide structure as an acyclic peptide modification, or as a side‐chain constraint to give a macrocycle.
No related grants have been discovered for Denis Scanlon.