68 research outputs found
The GPI Anchor Signal Sequence Dictates the Folding and Functionality of the Als5 Adhesin from Candida albicans
Background: Proteins destined to be Glycosylphosphatidylinositol (GPI) anchored are translocated into the ER lumen completely before the C-terminal GPI anchor attachment signal sequence (SS) is removed by the GPI-transamidase and replaced by a pre-formed GPI anchor precursor. Does the SS have a role in dictating the conformation and function of the protein as well? Methodology/Principal Findings: We generated two variants of the Als5 protein without and with the SS in order to address the above question. Using a combination of biochemical and biophysical techniques, we show that in the case of Als5, an adhesin of C. albicans, the C-terminal deletion of 20 amino acids (SS) results in a significant alteration in conformation and function of the mature protein. Conclusions/Significance: We propose that the locking of the conformation of the precursor protein in an alternate conformation from that of the mature protein is one probable strategy employed by the cell to control the behaviour an
Nucleic acid related compounds. 57. Synthesis, X-ray crystal structure, lipophilic partition properties, and antiretroviral activities of anomeric 3'-azido-2',3'-dideoxy-2,6-diaminopurine ribosides
Trimethylsilyl triflate-catalyzed transfer glycosylation of 2,6-diamino-9-(3-azido-2,3-dideoxy-alpha- and -beta-D-erythro-pentofuranosyl)purines (3 and 4) in low yields. Selective 2'-O-tosylation of 2,6-diamino-9-(beta-D-ribofuranosyl)purine (2,6-diaminopurine riboside, DAPR, 5) followed by our lithium triethylborohydride promoted 1,2-hydride rearrangement gave 2,6-diamino-9-(2-deoxy-beta-D-threo-pentofuranosyl)purine (7). Tritylation of 7 followed by mesylation at O3', deprotection, and displacement of the 3'-mesylate with azide provided a stereodefined synthesis of 2,6-diamino-9-(3-azido-2, 3-dideoxy-beta-D-erythro-pentofuranosyl)purine (AzddDAPR, 4). X-ray crystallographic analysis of 4 showed two orientations of the azido group, but consistent conformational features in the remainder of the molecule. In contrast, two independent conformations have been found for AZT. The azido function confers enhanced lipophilicity, which could be expected to contribute significantly to nonselective transport across membranes. A large difference in the octanol/water partition coefficients of the alpha (3) and beta (4) anomers wes found. The beta anomer (4) exerts potent inhibition of HIV-induced cytopathogenicity in human MT-4 cells (ED50: 0.3 microM). This concentration is an order of magnitude lower than that required for ddDAPR, AzddAdo, and AzddGuo. Potent inhibition of Moloney sarcoma virus induced transformation of murine C3H cells by AzddDAPR (4) was also observed. The alpha anomer (3) had no observed antiviral activity.status: publishe
Konformationsanalyse von Thiakronenether-Derivaten mit Hilfe von NMR Spektroskopie und molek�lmechanischen Berechnungen
When Practical Help is Valued so Much by Older People, Why do Professionals Fail to Recognise its Value?
What makes weekend allied health services effective and cost-effective (or not) in acute medical and surgical wards? Perceptions of medical, nursing, and allied health workers
Brain SPECT in the behaviourally disordered dog
Dogs can be used as research models in order to contribute to a better understanding of human neuropsychiatric disorders and to explore treatment options. In general, smaller laboratory animals, most often mice and rats, have been extensively used. Nevertheless, the implementation of larger animal (e.g. dogs) models has several important advantages. Their larger brain size omits the need for dedicated equipment (micro-PET or micro-SPECT), and the larger portion of the frontal cortex (crucial to behaviour regulation) in particular allows superior investigation of this area. They can further be used to investigate normal physiology and interaction of several neurotransmitter systems and the effects of drugs on brain function and chemistry. In this regard, they can also be used to obtain information on the pharmacokinetics and pharmacodynamics of newly developed drugs and the dosage at which maximal response and least side effects occur. Finally, natural animal behavioural models of disorders can be used to enlighten the biological base of several human neuropsychiatric disorders. In this chapter, an overview will be provided on the use of functional brain imaging in dogs suffering from impulsive aggression
Prefrontal Neurons Encode Actions and Outcomes in Conjunction with Spatial Location in Rats Performing a Dynamic Delayed Non-Match to Position Task
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