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Biophysical and structural studies on the capsid protein of the human immunodeficiency virus type 1: a new drug target?

Neira JL

Instituto de Biología Molecular y Celular, Universidad Miguel Hernández, Elche (Alicante) 03202, Spain. jlneira@umh.es

New therapeutic agents are necessary against HIV due to the rapid emergence of drug-resistant variants of the virus, which has yielded therapeutic strategies partially ineffective. Assembly can be considered as a good target for antivirals since it depends only on repetitive weak protein-protein interactions, and probably disruption of a small part of these interactions is sufficient to suppress infectivity in a dominant-negative effect. We propose the capsid protein of HIV-1 as a potential candidate.

Published 1 June 2009 in ScientificWorldJournal, 9: 404-19.
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Articles on Pharmacology published 1 June 2009:

Development of pharmacotherapies for drug addiction: a Rosetta stone approach.   Nat Rev Drug Discov, 8(6): 500-15.

Current pharmacotherapies for addiction represent opportunities for facilitating treatment and are forming a foundation for evaluating new medications. Furthermore, validated animal models of addiction and a surge in understanding of neurocircuitry and neuropharmacological mechanisms involved in the development and maintenance of addiction - such as the neuroadaptive changes that account for the transition to dependence and the vulnerability to relapse - have provided numerous potential ... [Abstract] [Full-text]

Structures of glycinamide ribonucleotide transformylase (PurN) from Mycobacterium tuberculosis reveal a novel dimer with relevance to drug discovery.   J Mol Biol, 389(4): 722-33.

Enzymes from the de novo purine biosynthetic pathway have been exploited for the development of anti-cancer drugs, and represent novel targets for anti-bacterial drug development. In Mycobacterium tuberculosis, the cause of tuberculosis, this pathway has been identified as essential for growth and survival. The structure of M. tuberculosis PurN (MtPurN) has been determined in complex with magnesium and iodide at 1.30 A resolution, and with cofactor analogue, 5-methyltetrahydrofolate (5MTHF) at ... [Abstract] [Full-text]

Fluorinated carbohydrates as lectin ligands: versatile sensors in 19F-detected saturation transfer difference NMR spectroscopy.   Chemistry, 15(23): 5666-8.

As a novel approach for studying carbohydrate-lectin interactions spectroscopically, we combine the resolution and specificity of (19)F-detected NMR spectroscopy with the sensitivity of the saturation transfer difference (STD) technique. The resulting background-free (19)F-STD spectra open a promising perspective for broad application with medical relevance, for example, in drug discovery. [Abstract] [Full-text]

Articles on Pharmacology published 29 May 2009:

Pharmacology and pharmacogenetics of chemotherapeutic agents.   Cancer Invest, 27(5): 482-8.

The last decade the field of oncology has seen the introduction of several efficacious chemotherapeutic agents. However the benefits achieved have been modest at best. The choice of chemotherapeutic agent is often empirical and geared to fit the average patient with the result that approximately 40% of patients may be receiving the wrong drug. With greater understanding of the mechanisms behind the heterogeneity observed across patient populations, both in terms of efficacy and toxicity of a ... [Abstract] [Full-text]

Comparative genome-scale metabolic reconstruction and flux balance analysis of multiple Staphylococcus aureus genomes identify novel antimicrobial drug targets.   J Bacteriol, 191(12): 4015-24.

Mortality due to multidrug-resistant Staphylococcus aureus infection is predicted to surpass that of human immunodeficiency virus/AIDS in the United States. Despite the various treatment options for S. aureus infections, it remains a major hospital- and community-acquired opportunistic pathogen. With the emergence of multidrug-resistant S. aureus strains, there is an urgent need for the discovery of new antimicrobial drug targets in the organism. To this end, we reconstructed the metabolic ... [Abstract] [Full-text]

Articles on Pharmacology published 28 May 2009:

Gastric cancer in the era of molecularly targeted agents: current drug development strategies.   J Cancer Res Clin Oncol, 135(7): 855-66.

Gastric cancer is the second most common cause of cancer death worldwide with approximately one million cases diagnosed annually. Despite considerable improvements in surgical techniques, innovations in clinical diagnostics and the development of new chemotherapy regimens, the clinical outcome for patients with advanced gastric cancer and cancer of the GEJ is generally poor with 5-year survival rates ranging between 5 and 15%. The understanding of cancer relevant events has resulted in new ... [Abstract] [Full-text]

Articles on Pharmacology published 26 May 2009:

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The important chemotherapeutic agents, Prontosil and pentenylpenicillin (penicillin F), were investigated initially by two men, Domagk and Fleming, who had been influenced by the horrendous wound infections of World War I. The very different pathways leading to their development and to that of the successor antibacterials (sulfa drugs, further penicillins, semi-synthetic penicillins), including the role played by patents, are discussed. [Abstract] [Full-text]

Articles on Pharmacology published 22 May 2009:

Targeting protein serine/threonine phosphatases for drug development.   Mol Pharmacol, 75(6): 1249-61.

With the recent clinical success of drugs targeting protein kinase activity, drug discovery efforts are focusing on the role of reversible protein phosphorylation in disease states. The activity of protein phosphatases, enzymes that oppose protein kinases, can also be manipulated to alter cellular signaling for therapeutic benefits. In this review, we present protein serine/threonine phosphatases as viable therapeutic targets, discussing past successes, current challenges, and future strategies ... [Abstract] [Full-text]

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