Tzong-Hsien Lee, James W Checco, Tess Malcolm, Chelcie H Eller, Ronald T Raines, Samuel H Gellman, Erinna F Lee, W Douglas Fairlie, Marie-Isabel Aguilar
{"title":"Differential membrane binding of α/β-peptide foldamers: implications for cellular delivery and mitochondrial targeting.","authors":"Tzong-Hsien Lee, James W Checco, Tess Malcolm, Chelcie H Eller, Ronald T Raines, Samuel H Gellman, Erinna F Lee, W Douglas Fairlie, Marie-Isabel Aguilar","doi":"10.1071/ch23063","DOIUrl":"https://doi.org/10.1071/ch23063","url":null,"abstract":"<p><p>The intrinsic pathway of apoptosis is regulated by the Bcl-2 family of proteins. Inhibition of the anti-apoptotic members represents a strategy to induce apoptotic cell death in cancer cells. We have measured the membrane binding properties of a series of peptides, including modified α/β-peptides, designed to exhibit enhanced membrane permeability to allow cell entry and improved access for engagement of Bcl-2 family members. The peptide cargo is based on the pro-apoptotic protein Bim, which interacts with all anti-apoptotic proteins to initiate apoptosis. The α/β-peptides contained cyclic β-amino acid residues designed to increase their stability and membrane-permeability. Dual polarisation interferometry was used to study the binding of each peptide to two different model membrane systems designed to mimic either the plasma membrane or the outer mitochondrial membrane. The impact of each peptide on the model membrane structure was also investigated, and the results demonstrated that the modified peptides had increased affinity for the mitochondrial membrane and significantly altered the structure of the bilayer. The results also showed that the presence of an RRR motif significantly enhanced the ability of the peptides to bind to and insert into the mitochondrial membrane mimic, and provide insights into the role of selective membrane targeting of peptides.</p>","PeriodicalId":8575,"journal":{"name":"Australian Journal of Chemistry","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10540276/pdf/nihms-1928984.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41105277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Julia Y. Wang, Wei Zhang, Michael W. Roehrl, Victor B. Roehrl, Michael H. Roehrl
{"title":"An autoantigen profile from Jurkat T-Lymphoblasts provides a molecular guide for investigating autoimmune sequelae of COVID-19","authors":"Julia Y. Wang, Wei Zhang, Michael W. Roehrl, Victor B. Roehrl, Michael H. Roehrl","doi":"10.1071/ch22268","DOIUrl":"https://doi.org/10.1071/ch22268","url":null,"abstract":"<p>In order to understand autoimmune phenomena contributing to the pathophysiology of COVID-19 and post-COVID syndrome, we have been profiling autoantigens (autoAgs) from various cell types. Although cells share numerous autoAgs, each cell type gives rise to unique COVID-altered autoAg candidates, which may explain the wide range of symptoms experienced by patients with autoimmune sequelae of SARS-CoV-2 infection. Based on the unifying property of affinity between autoAgs and the glycosaminoglycan dermatan sulfate (DS), this paper reports 140 candidate autoAgs identified from proteome extracts of human Jurkat T-cells, of which at least 105 (75%) are known targets of autoantibodies. Comparison with currently available multi-omic COVID-19 data shows that 125 (89%) DS-affinity proteins are altered at protein and/or RNA levels in SARS-CoV-2-infected cells or patients, with at least 94 being known autoAgs in a wide spectrum of autoimmune diseases and cancer. Protein alterations by ubiquitination and phosphorylation during the viral infection are major contributors of autoAgs. The autoAg protein network is significantly associated with cellular response to stress, apoptosis, RNA metabolism, mRNA processing and translation, protein folding and processing, chromosome organization, cell cycle, and muscle contraction. The autoAgs include clusters of histones, CCT/TriC chaperonin, DNA replication licensing factors, proteasome and ribosome proteins, heat shock proteins, serine/arginine-rich splicing factors, 14-3-3 proteins, and cytoskeletal proteins. AutoAgs, such as LCP1 and NACA, that are altered in the T cells of COVID patients may provide insight into T-cell responses to viral infection and merit further study. The autoantigen-ome from this study contributes to a comprehensive molecular map for investigating acute, subacute, and chronic autoimmune disorders caused by SARS-CoV-2.</p>","PeriodicalId":8575,"journal":{"name":"Australian Journal of Chemistry","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2023-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138510244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Julia Y. Wang, Wei Zhang, Victor B. Roehrl, Michael W. Roehrl, Michael H. Roehrl
{"title":"An autoantigen-ome from HS-Sultan B-Lymphoblasts offers a molecular map for investigating autoimmune sequelae of COVID-19","authors":"Julia Y. Wang, Wei Zhang, Victor B. Roehrl, Michael W. Roehrl, Michael H. Roehrl","doi":"10.1071/ch22267","DOIUrl":"https://doi.org/10.1071/ch22267","url":null,"abstract":"<p>To understand how COVID-19 may induce autoimmune diseases, we have been compiling an atlas of COVID autoantigens (autoAgs). Using dermatan sulfate (DS) affinity enrichment of autoantigenic proteins extracted from HS-Sultan lymphoblasts, we identified 362 DS-affinity proteins, of which at least 201 (56%) are confirmed autoAgs. Comparison with available multi-omic COVID data shows that 315 (87%) of the 362 proteins are affected in SARS-CoV-2 infection via altered expression, interaction with viral components, or modification by phosphorylation or ubiquitination, at least 186 (59%) of which are known autoAgs. These proteins are associated with gene expression, mRNA processing, mRNA splicing, translation, protein folding, vesicles, and chromosome organization. Numerous nuclear autoAgs were identified, including both classical antinuclear antibodies (ANAs) and extractable nuclear antigens (ENAs) of systemic autoimmune diseases and unique autoAgs involved in the DNA replication fork, mitotic cell cycle, or telomerase maintenance. We also identified many uncommon autoAgs involved in nucleic acid and peptide biosynthesis and nucleocytoplasmic transport, such as aminoacyl-tRNA synthetases. In addition, this study found autoAgs that potentially interact with multiple SARS-CoV-2 Nsp and Orf components, including CCT/TriC chaperonin, insulin degrading enzyme, platelet-activating factor acetylhydrolase, and the ezrin-moesin-radixin family. Furthermore, B-cell-specific IgM-associated endoplasmic reticulum (ER) complex (including MBZ1, BiP, heat shock proteins, and protein disulfide-isomerases) is enriched by DS-affinity and up-regulated in B-cells of COVID-19 patients, and a similar IgH-associated ER complex was also identified in autoreactive pre-B1 cells in our previous study, which suggests a role of autoreactive B1 cells in COVID-19 that merits further investigation. In summary, this study demonstrates that virally infected cells are characterized by alterations of proteins with propensity to become autoAgs, thereby providing a possible explanation for infection-induced autoimmunity. The COVID autoantigen-ome provides a valuable molecular resource and map for investigation of COVID-related autoimmune sequelae and considerations for vaccine design.</p>","PeriodicalId":8575,"journal":{"name":"Australian Journal of Chemistry","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2023-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138510251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Psychedelic medicines","authors":"M. Piggott, P. Duggan","doi":"10.1021/cen-09413-cover","DOIUrl":"https://doi.org/10.1021/cen-09413-cover","url":null,"abstract":"","PeriodicalId":8575,"journal":{"name":"Australian Journal of Chemistry","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2023-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76187912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gang Chen, Chang-Hong Yu, Xin Lv, Bing Qiu, Wei Jiang
{"title":"Retraction notice to ‘Crystal Structures and Anti-Colon Cancer Activity of Two Lanthanide Complexes with O-Donor Diacetone Ligands’ [Australian Journal of Chemistry (2019) doi:10.1071/CH18568]","authors":"Gang Chen, Chang-Hong Yu, Xin Lv, Bing Qiu, Wei Jiang","doi":"10.1071/ch18568_re","DOIUrl":"https://doi.org/10.1071/ch18568_re","url":null,"abstract":"","PeriodicalId":8575,"journal":{"name":"Australian Journal of Chemistry","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2023-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74389229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
David Jago, D. C. Milan, A. Sobolev, S. Higgins, A. Vezzoli, R. Nichols, George A. Koutsantonis
{"title":"Evaluation of the 5-ethynyl-1,3,3-trimethyl-3H-indole ligand for molecular materials applications","authors":"David Jago, D. C. Milan, A. Sobolev, S. Higgins, A. Vezzoli, R. Nichols, George A. Koutsantonis","doi":"10.1071/ch23069","DOIUrl":"https://doi.org/10.1071/ch23069","url":null,"abstract":"The modification of conjugated organic compounds with organometallic moieties allows the modulation of the electronic and optoelectronic properties of such compounds and lends them to a variety of material applications. The organometallic complexes [M(Cp′)(L)n] (M = Ru or Fe; Cp′ = cyclopentadiene (Cp) or pentamethylcyclopentadiene (Cp*); (L)n = (PPh3)2 or 1,2-bi(diphenylphosphino)ethane (dppe)) and [M(L)n] (M = Ru; (L)n = (dppe)2 or (P(OEt)3)4; or M = Pt; (L)n = (PEt3)2, (PPh3)2 or tricyclohexylphosphine, (PCy3)2) modified with a 5-ethynyl-1,3,3-trimethyl-3H-indole ligand were prepared and characterised by NMR spectroscopy, IR and single-crystal X-ray diffraction. Cyclic voltammetry and IR spectroelectrochemistry of the ruthenium systems showed a single-electron oxidation localised over the M–C≡C–aryl moiety. The N-heteroatom of the indole ligand showed Lewis base properties and was able to extract a proton from a vinylidene intermediate as well as coordinate to CuI. Examples from the wire-like compounds were also studied by single-molecule break junction experiments but molecular junction formation was not observed. This is most likely attributable to the binding characteristics of the substituted terminal indole groups used here to the gold contacts.","PeriodicalId":8575,"journal":{"name":"Australian Journal of Chemistry","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2023-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88914030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L. Sun, Siying An, Dong Wei, Ronglan Zhang, Jian-she Zhao
{"title":"PhotoCORMs based on zinc(ii)-flavonol derivatives with superior biological properties for use in living organisms","authors":"L. Sun, Siying An, Dong Wei, Ronglan Zhang, Jian-she Zhao","doi":"10.1071/ch22243","DOIUrl":"https://doi.org/10.1071/ch22243","url":null,"abstract":"CO is an important gas signal molecule and plays an indispensable role in the maintenance of cell homeostasis. Herein, photoinduced CO-releasing molecules (photoCORMs), that combine the effects of zinc(ii) and different ligands including flavonol derivatives and tripod pyridyl compounds, are reported. The photoCORMs can release about one equivalent of CO, and the solid samples are stabile for more than 90 days in air. Cytotoxicity tests suggest that photoCORMs possess low toxicity and have the potential to be used in organisms. The intracellular uptake and photoreactivity of photoCORM 3a, with low toxicity and a rapid CO-release rate, were studied in HeLa cells. The results indicate that 3a could successfully penetrate the cell membrane and enter the cytoplasm. More importantly, it is further demonstrated that 3a can successfully release CO in HeLa cells, which is detected using intracellular CO sensors. Based on the cell study, the same result was found when the photoinduced CO release of 3a in Kunming mice was studied utilizing a carboxyhemoglobin kit. This study is of great significance for the development of new valuable CO donors that can be applied to organisms to exert their biological effects.","PeriodicalId":8575,"journal":{"name":"Australian Journal of Chemistry","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2023-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89628274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Palladium-mediated CO 2 extrusion followed by insertion of ketenes: translating mechanistic studies to develop a one-pot method for the synthesis of ketones","authors":"Yang Yang, Allan J. Canty, Richard A. J. O’Hair","doi":"10.1071/ch23026","DOIUrl":"https://doi.org/10.1071/ch23026","url":null,"abstract":"<p>Multistage mass spectrometry (MS<sup><i>n</i></sup>) experiments were used to explore extrusion–insertion (ExIn) reactions of the palladium complex [(phen)Pd(O<sub>2</sub>CPh)]<sup>+</sup> (phen, 1,10-phenanthroline). Under collision-induced dissociation (CID) conditions, the organopalladium cation [(phen)Pd(Ph)]<sup>+</sup> was formed via decarboxylation and was found to react with phenylmethylketene to yield the enolate [(phen)Pd(CPhMeC(O)Ph)]<sup>+</sup> via an insertion reaction. A further stage of CID revealed that the enolate fragments via loss of styrene to form the acyl complex [(phen)Pd(C(O)Ph)]<sup>+</sup>. Formation of both the coordinated enolate and acyl anions is supported by density functional theory (DFT) calculations. Attempts to develop a palladium-mediated one-pot synthesis of ketones from 2,6-dimethoxybenzoic acid as the key substrate and the ketene substrates R<sup>1</sup>R<sup>2</sup>C═C═O (R<sup>1</sup> = Ph, R<sup>2</sup> = Me; R<sup>1</sup> = R<sup>2</sup> = Ph) proved challenging owing to low yields and side product formation.</p>","PeriodicalId":8575,"journal":{"name":"Australian Journal of Chemistry","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2023-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138510224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nonlinear optics: from theory to applications, with a focus on the use of two-photon absorption in biology","authors":"Mélanie Dréano, O. Mongin, F. Paul, M. Humphrey","doi":"10.1071/ch23015","DOIUrl":"https://doi.org/10.1071/ch23015","url":null,"abstract":"The study of nonlinear optics in the 1960s attracted considerable attention from a theoretical standpoint, engendering many proposals for practical use of these new photonic effects. Among these suggestions, the development of efficient two-photon absorption (2PA) has attracted sustained interest due to its demonstrated (or potential) use in a broad range of applications that include optical data storage, optical limiting and nanofabrication. The use of 2PA in biological applications is particularly appealing. This is because 2PA offers several advantages for bio-oriented applications, such as intrinsic three-dimensional resolution, increased penetration depth in biological materials such as tissue and highly focused excitation at half-energy, leading to a decrease of auto-fluorescence and photodamage. In this Primer Review, we introduce the essential background theory needed for an understanding of the field, we describe the key experiments deployed to quantify material performance, we discuss the evolution of 2PA molecular design, and we summarise the state-of-the-art and the existing challenges in the use of 2PA in imaging, therapy and theranostics.","PeriodicalId":8575,"journal":{"name":"Australian Journal of Chemistry","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2023-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78093205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Bhosale, S. Bhosale, M. Kalyankar, S. Langford, Ceilica H. Lalander
{"title":"Retraction notice to ‘Self-Assembly of Protoporphyrin IX-TEG Derivatives into Tunable Nanoscaled Spherical Structures’ [Australian Journal of Chemistry 63(9) (2010), 1326–1329. doi:10.1071/CH10199]","authors":"S. Bhosale, S. Bhosale, M. Kalyankar, S. Langford, Ceilica H. Lalander","doi":"10.1071/ch10199_re","DOIUrl":"https://doi.org/10.1071/ch10199_re","url":null,"abstract":"","PeriodicalId":8575,"journal":{"name":"Australian Journal of Chemistry","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2023-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79231494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}