Worldwide, there are plants known as psychoactive plants that naturally contain psychedelic active components. They have a high concentration of neuroprotective substances that can interact with the nervous system to produce psychedelic effects. Despite these plants' hazardous potential, recreational use of them is on the rise because of their psychoactive properties. Early neuroscience studies relied heavily on psychoactive plants and plant natural products (NPs), and both recreational and hazardous NPs have contributed significantly to the understanding of almost all neurotransmitter systems. Worldwide, there are many plants that contain psychoactive properties, and people have been using them for ages. Psychoactive plant compounds may significantly alter how people perceive the world.
1. Biochemistry. 2012 Sep 25;51(38):7638-50. doi: 10.1021/bi301017s. Epub 2012 Sep 14. Mapping the active site helix-to-strand conversion of CxxxxC peroxiredoxin Q enzymes. Perkins A(1), Gretes MC, Nelson KJ, Poole LB, Karplus PA. Author information: (1)Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA. Peroxiredoxins (Prx) make up a family of enzymes that reduce peroxides using a peroxidatic cysteine residue; among these, members of the PrxQ subfamily are proposed to be the most ancestral-like yet are among the least characterized. In many PrxQ enzymes, a second "resolving" cysteine is located five residues downstream from the peroxidatic Cys, and these residues form a disulfide during the catalytic cycle. Here, we describe three hyperthermophilic PrxQ crystal structures originally determined by the RIKEN structural genomics group. We reprocessed the diffraction data and conducted further refinement to yield models with R(free) values lowered by 2.3-7.2% and resolution extended by 0.2-0.3 Å, making one, at 1.4 Å, one of the best resolved peroxiredoxins to date. Comparisons of two matched thiol and disulfide forms reveal that the active site conformational change required for disulfide formation involves a transition of ~20 residues from a pair of α-helices to a β-hairpin and 3(10)-helix. Each conformation has ~10 residues with a high level of disorder providing slack that allows the dramatic shift, and the two conformations are anchored to the protein core by distinct nonpolar side chains that fill three hydrophobic pockets. Sequence conservation patterns confirm the importance of these and a few additional residues for function. From a broader perspective, this study raises the provocative question of how to make use of the valuable information in the Protein Data Bank generated by structural genomics projects but not described in the literature, perhaps remaining unrecognized and certainly underutilized. DOI: 10.1021/bi301017s PMCID: PMC3549014 PMID: 22928725 [Indexed for MEDLINE] 2. (68)Ga-Labeled β-aminoalanine, γ-aminohomoalanine, and ε-aminolysine conjugates of 1,4,7-triazacyclononane-1,4,7-triacetic acid. Shan L(1). In: Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004–2013. 2011 Aug 29 [updated 2011 Oct 12]. Author information: (1)National Center for Biotechnology Information, NLM, NIH The 68Ga-labeled β-aminoalanine, γ-aminohomoalanine, and ε-aminolysine conjugates of 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA), abbreviated as 68Ga-1a, 68Ga-1b, and 68Ga-1c, respectively, were synthesized by Shetty et al. for positron emission tomography (PET) of tumors (1). Radiolabeled amino acids represent a diverse class of tracers that target the increased amino acid transport in cancer cells (2, 3). To date, >20 distinct amino acid transporters have been identified in mammalian cells, and these transporters differ in terms of substrate specificity, tissue expression patterns, sodium and other ion dependence, pH sensitivity, and transport mechanism (4, 5). Because of increased demand for amino acids in malignant cells, some transporters have been shown to be overexpressed in different types of tumors, and the process of amino acid transport is relatively fast (1, 2, 6). These features make tumor imaging with amino acid tracers possible within 20 min. Indeed, there is growing evidence that radiolabeled amino acids have the potential to overcome some of the limitations of 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) in tumor imaging, especially in the imaging of primary and recurrent brain tumors, neuroendocrine tumors, and prostate cancers (2, 3, 7). Different studies also showed that radiotracers that target different amino acid transporters exhibit different imaging properties that may provide unique biological information of tumors (1, 2, 8). The first group of widely investigated amino acids is the analogs of phenylalanine and tyrosine (2, 3). Because of their bulky neutral side chains, these natural amino acids are the substrates of system L transporters and have been proven to be useful for tumor imaging, particularly for brain tumors. The limitation common to most of the natural amino acids is the susceptibility to in vivo metabolism, which decreases tumor specificity and complicates kinetic analysis. Because none of the natural amino acids contain fluorine or iodine, labeling with fluorine-18 or iodine-123 while retaining identical biological activity is also difficult. These shortcomings associated with natural amino acids can be partially overcome by using non-natural amino acids. Typically, non-natural amino acids are neither metabolized nor readily incorporated into protein in vivo (1-3). One group of non-natural amino acids is α,α-dialkyl amino acids, which are generated by substituting the α-carbon hydrogen of natural amino acids with a methyl group or other alkyl chains. These amino acids are primarily the substrates of system A transporters. The second group is alicyclic amino acids, which are α,α-dialkyl amino acids with side chains bonded covalently to each other to form a cyclic ring. These amino acids are the substrates of system L transporters. The third group is the non-natural proline derivatives, which exhibit different transport selectivity. One challenge in developing amino acid radiotracers is to overcome the low selectivity and the decreased recognition after radiolabeling to specific transporters (2, 3, 8). Another challenge is the low uptake of amino acid agents in tumors, which leads to less sensitivity for tumor detection than with [18F]FDG (7). Shetty et al. synthesized a group of 68Ga-labeled alanine and lysine derivatives of NOTA, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), 1,4,7,10-tetraazacyclododecane-1,7-diacetic acid (DO2A), and 1,4,7,10-tetraazacyclododecane-1,4,7,-triacetic acid (DO3A) (1, 8). The four bifunctional chelating agents have similar sizes, but they differ in the net charges and stability because of the different numbers of pendent carboxylate arms. The amino acids have been conjugated to one of the carboxylate arms, and the nitrogen atoms in the heterocyclic ring are presumed to coordinate with metals to form chelates. Biodistribution studies and PET imaging indicate the structure–activity relationship of the amino acid derivatives, and the selective uptakes of these compounds by different cancer tissues might provide an insight on the different modes of amino acid uptake by cancer cells (1, 8). This chapter summarizes the data obtained with 68Ga-labeled NOTA derivatives: 68Ga-1a (68Ga-NOTA-β-aminoalanine), 68Ga-1b (68Ga-NOTA-γ-aminohomoalanine), and 68Ga-1c (68Ga-NOTA-ε-aminolysine). These NOTA derivatives were comparatively analyzed with the corresponding DOTA derivatives (68Ga-2a, 68Ga-2b, and 68Ga-2c, respectively) (1). PMID: 22013605 3. Tetrahedron. 2009 Mar 21;65(12):2399-2407. doi: 10.1016/j.tet.2009.01.028. Amphiphilic Dipyrrinones. Methoxylated [6]-Semirubins. Dey SK(1), Lightner DA. Author information: (1)Chemistry Department, University of Nevada, Reno, NV 89557-0216. Replacing the typical beta-alkyl substituents of [6]-semirubin and [6]-oxosemirubin, two intramolecularly hydrogen-bonded bilirubin analogs, with methoxy groups produces amphiphilic dipyrrinones. Synthesized from the respective 9H-dipyrrinones prepared by base-catalyzed condensation of 3,4-dimethoxypyrrolin-2-one with the appropriate pyrrole alpha-aldehyde, the 2,3-dimethoxy and 2,3,7,8-tetramethoxy analogs of [6]-semirubin are yellow-colored dipyrrinones that form intramolecularly hydrogen-bonded monomers in CDCl(3), as deduced from (1)H-NMR NH chemical shifts. They are monomeric in CHCl(3), as determined by vapor pressure osmometry. In contrast, in the solid, X-ray crystallography reveals supramolecular ribbons of intermolecularly hydrogen-bonded (dipyrrinone to dipyrrinone and acid to acid) 2,3,7,8-tetramethoxy-[6]-semirubin. The latter is approximately 20 times more soluble in water than the parent [6]-semirubin with four beta-methyl groups. DOI: 10.1016/j.tet.2009.01.028 PMCID: PMC2896323 PMID: 20606763 4. Cancer Lett. 1999 Apr 26;138(1-2):131-7. doi: 10.1016/s0304-3835(98)00386-3. Suppressive effects of alpha-Hederin on 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated murine Cyp1a-1 expression in the mouse hepatoma Hepa-1c1c7 cells. Jeong HG(1), Lee SS. Author information: (1)Department of Biological Science, Chosun University, Kwangju, South Korea. hgjeong@mail.chosun.ac.kr Cultured mouse hepatoma cell line Hepa-1c1c7 cells were treated with alpha-Hederin to assess the role of alpha-Hederin in the process of Cyp1a-1 induction. Treatment of Hepa-1c1c7 cultures with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced Cyp1a-1, as indicated by analysis of 7-ethoxyresorufin O-deethylation (EROD) activity and Cyp1a-1 protein. When alpha-Hederin and TCDD were both added to cultures, TCDD-inducible EROD activity was greatly suppressed by alpha-Hederin in a dose-dependent manner. TCDD-induced Cyp1a-1 protein and mRNA levels were markedly reduced in the concomitant treatment of TCDD and alpha-Hederin consistent with EROD activity. Electrophoretic mobility shift assay using nuclear extraction of cells revealed that alpha-Hederin reduced transformation of the Ah receptor to a form capable of specifically binding to an oligonucleotide containing a dioxin-response element (DRE) sequence of the Cyp1a-1 gene. These results suggest that the suppressive effect of alpha-Hederin on TCDD-induced Cyp1a-1 gene expression in Hepa-1c1c7 cells might be an antagonist of the DNA binding potential of a nuclear Ah receptor. DOI: 10.1016/s0304-3835(98)00386-3 PMID: 10378784 [Indexed for MEDLINE] 5. Toxicol Appl Pharmacol. 1990 Dec;106(3):418-32. doi: 10.1016/0041-008x(90)90337-t. TCDD-induced altered expression of growth factors may have a role in producing cleft palate and enhancing the incidence of clefts after coadministration of retinoic acid and TCDD. Abbott BD(1), Birnbaum LS. Author information: (1)National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is teratogenic in mice, inducing cleft palate and hydronephrosis at doses which are not overtly maternally toxic or embryotoxic. After TCDD exposure the palatal shelves of normal size come into contact, but fail to fuse due to altered differentiation of the medial epithelial cells. These cells continue to express EGF receptors, proliferate, and differentiate into an oral-like stratified squamous epithelium. The present study examines the effect of TCDD on the expression of growth factors which are believed to regulate differentiation and proliferation in the palate. This study also examined the combined effect of TCDD and retinoic acid (RA), since in teratology studies coadministration of these agents results in an enhancement of cleft palate incidence. Embryos were exposed in vivo on Gestation Day (GD) 10 or 12 to TCDD ot TCDD + RA and the palatal shelves were dissected on GD 14-16. Growth factor expression was determined immunohistochemically using antibodies to TGF-alpha, EGF, TGF-beta 1, or TGF-beta 2. The growth factors displayed specific spatial and temporal expression in the palatal shelves. TCDD reduced the expression of TGF-alpha, EGF, and TGF-beta 1 in epithelial and mesenchymal cells. The degree of reduction was generally greater after exposure on GD 10 to TCDD alone or in combination with RA when compared to that on GD 12. The abnormal proliferation and differentiation of TCDD-exposed medial cells may be a response to reduced expression of EGF and TGF-alpha. Low levels of these factors may be related to the previously observed elevated levels of EGF receptors in medial cells. In other systems, low levels of ligand have resulted in upregulation of the EGF receptor. Continued proliferation and altered differentiation could also be attributable to decreased levels of TGF-beta 1, a factor inhibitory to epithelial proliferation. Since TGF-beta 1 stimulates mesenchymal growth and TGF-alpha and EGF stimulate epithelial proliferation, the formation of small shelves after exposure to TCDD + RA on GD 10 may be due to the severe reduction in these factors. Only a slight to moderate reduction in growth factor expression occurs after exposure to TCDD + RA on GD 12 and in this case shelves of normal size form. Since TCDD and RA appear to act in part through pathways that involve TGF-beta 1, in vitro experiments were designed to examine the involvement of TGF-beta 1 in TCDD teratogenicity.(ABSTRACT TRUNCATED AT 400 WORDS) DOI: 10.1016/0041-008x(90)90337-t PMID: 2260090 [Indexed for MEDLINE]