Search results for "MIM"
showing 10 items of 645 documents
Optimization Strategy of Novel Peptide-Based Michael Acceptors for the Treatment of Human African Trypanosomiasis
2019
This paper describes an optimization strategy of the highly active vinyl ketone 3 which was recognized as a strong inhibitor of rhodesain of Trypanosoma brucei rhodesiense, endowed with a ksecond v...
Development of Novel Benzodiazepine-Based Peptidomimetics as Inhibitors of Rhodesain from Trypanosoma brucei rhodesiense.
2020
Starting from the reversible rhodesain inhibitors 1 a-c, which have Ki values towards the target protease in the low-micromolar range, we have designed a series of peptidomimetics, 2 a-g, that contain a benzodiazepine scaffold as a β-turn mimetic; they are characterized by a specific peptide sequence for the inhibition of rhodesain. Considering that irreversible inhibition is strongly desirable in the case of a parasitic target, a vinyl ester moiety acting as Michael-acceptor was introduced as the warhead; this portion was functionalized in order to evaluate the size of corresponding enzyme pocket that could accommodate this substituent. With this investigation, we identified an irreversibl…
Synthesis and biological evaluation of papain-family cathepsin L-like cysteine protease inhibitors containing a 1,4-benzodiazepine scaffold as antipr…
2014
Novel papain-family cathepsin L-like cysteine protease inhibitors endowed with antitrypanosomal and antimalarial activity were developed, through an optimization study of previously developed inhibitors. In the present work, we studied the structure-activity relationships of these derivatives, with the aim to develop new analogues with a simplified and more synthetically accessible structure and with improved antiparasitic activity. The structure of the model compounds was significantly simplified by modifying or even eliminating the side chain appended at the C3 atom of the benzodiazepine scaffold. In addition, a simple methylene spacer of appropriate length was inserted between the benzod…
Longitudinal analysis of Mycobacterium tuberculosis 19-kDa antigen-specific T cells in patients with pulmonary tuberculosis: association with disease…
2003
CD8(+) T cells play a central role in immune protection against infection with Mycobacterium tuberculosis. One of the target epitopes for anti-M. tuberculosis directed CD8(+) T cells is the HLA-A2-restricted 19-kDa lipoprotein peptide VLTDGNPPEV. T cell clones directed against this epitope recognized not only the nominal peptide ligand, but also a closely related peptide (VPTDPNPPEV) from the HIV envelope gp120 (HIV(env) gp120) protein characterized by IFN-gamma release. This cross-reactivity was confirmed in ex vivo in M. tuberculosis 19-kDa tetramer-sorted T cells from patients with tuberculosis and in HIVgp120 tetramer-reactive T cells sorted from HIV(+) patients. M. tuberculosis 19-kDa …
Fasting renders immunotherapy effective against low-immunogenic breast cancer while reducing side effects
2022
Immunotherapy is improving the prognosis and survival of cancer patients, but despite encouraging out-comes in different cancers, the majority of tumors are resistant to it, and the immunotherapy combinations are often accompanied by severe side effects. Here, we show that a periodic fasting-mimicking diet (FMD) can act on the tumor microenvironment and increase the efficacy of immunotherapy (anti-PD-L1 and anti-OX40) against the poorly immunogenic triple-negative breast tumors (TNBCs) by expanding early exhausted effector T cells, switching the cancer metabolism from glycolytic to respiratory, and reducing collagen depo-sition. Furthermore, FMD reduces the occurrence of immune-related adve…
Onomatopeya, imitación y poesía en Grecia y Roma
2019
A partir de Platón se desarrolla en la reflexión gramatical y filosófica griega la idea de que ciertos vocablos tienen un origen onomatopéyico, tomándose como modelo de su uso (tanto por su conveniencia como por su condena) su aparición en el epos homérico. Mientras la filosofía vinculará tales palabras, entendidas como onomatopeyas, al origen del lenguaje, los autores de poética y gramática las estudiarán como elementos significativos en la valoración estética de la poesía. La doctrina griega sobre la onomatopeya pasará, a su vez, a las letras latinas.
Funcionalizaciones estereoselectivas de iminolactonas quirales: aplicación a la síntesis de peptidomiméticos
2012
En los últimos años, la elucidación del genoma humano y el descubrimiento de péptidos con importantes actividades biológicas tales como hormonas, neurotransmisores y neuromoduladores, ha provocado un aumento en el interés del uso de este tipo de moléculas con fines terapéuticos. Sin embargo el uso de péptidos como fármacos presenta numerosos inconvenientes: - Tienen poca estabilidad metabólica al ser susceptibles de proteólisis por la acción de diferentes proteasas. - Son rápidamente eliminados a través del hígado y riñón. - Presentan una baja biodisponibilidad en fluidos biológicos. - Su elevada flexibilidad conformacional les dificulta conferir la estructura secundaria bioactiva. En este …
Nitric oxide increases the decay of matrix metalloproteinase 9 mRNA by inhibiting the expression of mRNA-stabilizing factor HuR.
2003
Dysregulation of extracellular matrix turnover is an important feature of many inflammatory processes. Rat renal mesangial cells express high levels of matrix metalloproteinase 9 (MMP-9) in response to inflammatory cytokines such as interleukin-1 beta. We demonstrate that NO does strongly destabilize MMP-9 mRNA, since different luciferase reporter gene constructs containing the MMP-9 3' untranslated region (UTR) displayed significant reduced luciferase activity in response to the presence of NO. Moreover, by use of an in vitro degradation assay we found that the cytoplasmic fractions of NO-treated cells contained a higher capacity to degrade MMP-9 transcripts than those obtained from contro…
Core and Accessory Genome Analysis of Vibrio mimicus
2021
© 2021 by the authors.
On the Statistical Analysis of the Channel Capacity of Double Rayleigh Channels with Equal Gain Combining in V2V Communication Systems
2010
paper presented at the 2010 IEEE 71st Vehicular Technology Conference, Taipei. (c) 2010 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other users, including reprinting/ republishing this material for advertising or promotional purposes, creating new collective works for resale or redistribution to servers or lists, or reuse of any copyrighted components of this work in other works. Paper also available from the publisher: http://dx.doi.org/10.1109/VETECS.2010.5494112 In this article, we present a detailed study on the statistical properties of the channel capacity of vehicle-to-vehicle (V2V) fading channels with equal gain combining (EGC). A…