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Evidence for a Role of Infections in the Activation of Autoreactive T Cells and the Pathogenesis of Autoimmunity
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
J. Ludovic Croxford, Stephen D. Miller
Chagas disease is a form of heart disease linked to inflammatory cardiomyopathy, and occurs in individuals chronically infected with Trypanosoma cruzi. The continuation of disease in the supposed absence of parasitic infiltration has led to the proposal that Chagas disease has an autoimmune component.47 A number of studies have described potential cross-reactive sequences between T. cruzi and numerous cardiac antigens such as cardiac myosin, mammalian nerve, ribonucleoprotein, microtubule-associated protein of the cytoskeleton and the β1-adrenergic receptor, suggesting that T. cruzi infection may induce an immune response towards self-tissue via molecular mimicry.48-51 Furthermore, T cells isolated from the hearts of Chagas patients were reactive to both cardiac myosin heavy chain and a T. cruzi antigen, as measured by proliferation and Th1 cytokine production.47 However, in most cases the evidence for a role of molecular mimicry in Chagas disease is circumstantial. An alternative theory suggests that it is the persistent infection by the parasite in the target organ, which induces chronic inflammation and leads to tissue damage.52
Biocatalysts: The Different Classes and Applications for Synthesis of APIs
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
More than 10 years earlier, Baeckvall and his group (Pàmies and Baeckvall, 2001) developed an efficient kinetic resolution of racemic β-hydroxy nitriles via Candida antarctica lipase (Novozyme-435)-catalyzed transesterification in toluene at 80°C with 4-chlorophenyl acetate as acylating agent. A variety of racemic alkyl, aryl, and aryloxymethyl substituted β-hydroxy nitriles was efficiently transformed to the corresponding enantiomerically pure acetates. The combination with a Ru-complex-catalyzed alcohol racemization led to a DKR enabling the synthesis of enantiomerically pure acetates with ee’s up to 99%, and yields up to 85%. Examples are the synthesis of Denopamine and Propanolol precursors (see the below scheme). Denopamine is an orally administered drug acting as a β1 adrenergic receptor (ADRB1) agonist and used to treat angina as well as congestive heart failure and for clearing pulmonary edema. Propranolol, already detected 1964, belongs to the drug class of non-selective beta blockers. It is used to treat among others high blood pressure, cardiovascular hypertension, angina pectoris, tachyarrhythmia, myocardial infarction, or tachycardia and is administered intravenously or orally. The drug is on the World Health Organization’s List of Essential Medicines (WHO Model List of Essential Medicines (19th List)”; World Health Organization. April 2015).
Simulative structure and binding sites of lyral with olfactory receptor 10J5 using computational prediction methods
Published in Journal of Toxicology and Environmental Health, Part A, 2020
Pu Wang, Rui Zhang, Shunbang Yu, Charles Lee, He Wang
The amino acid sequence for OR10J5 (GenBank: ALI87606.1) was obtained from the National Center for Biotechnology Information (NCBI, http://www.ncbi.nlm.nih.gov) database. Subsequently, several G protein coupled receptors (GPCRs) that exhibited relatively high similarity with OR10J5 were searched using Blastp at a setting of “non-redundant protein sequences.” Based upon the identity results, these were compared with OR10J5, and the following were found: bovine rhodopsin (13%), human β2 adrenergic receptor (23%), turkey β1 adrenergic receptor (22%), human CXCR4 chemokine receptor (22%), human histamine receptor H1 (11%), human adenosine A2a receptor (14%), and human dopamine D3 receptor (10%). In addition, the positive amino acids of bovine rhodopsin identified reached 31%, which indicated that this value was above the threshold required for safe homology modeling of 30% for OR10J5 in protein structure (Sander and Schneider 1991). Further, Pilpel and Lancet (1999) and Schmiedeberg et al. (2007) employed bovine rhodopsin in homology models of GPCRs. Therefore, bovine rhodopsin with 2.8Å resolution was selected as the experimental template, and the human β2 adrenergic receptor was selected as the validate template.