Current Pharmaceutical Biotechnology - Volume 12, Issue 10, 2011

Therapeutic proteins produced using recombinant DNA technologies are generally complex, heterogeneous, and subject to a variety of enzymatic or chemical modifications during expression, purification, and long-term storage. Hence the analytical strategies for characterization, quantitation, purity assay and evaluation of the biological activity of recombinant proteins still represent a big challenge and a matter for debate. The Read More

Most of the protein therapeutics are now produced by recombinant DNA technology. The advantages of recombinant proteins are related to their higher specificity and to their safety as exposure to animal or human diseases. However, several problems are still present in development of recombinant proteins as therapeutics, such as low bioavailability, short serum half-life, and immune response. Their successful applicati Read More

Mass spectrometry has already become an indispensable tool in the analytical armamentarium of the biopharmaceutical industry, although its current uses are limited to characterization of covalent structure of recombinant protein drugs. However, the scope of applications of mass spectrometry-based methods is beginning to expand to include characterization of the higher order structure and dynamics of biophar Read More

Production of protein-based pharmaceuticals is a major issue in conventional pharmacology, biomedicine and nanomedicine. Being mostly obtained by genetic engineering, the quality and activity of protein drugs is a steady matter of concern. Although the physiology of the host recombinant cells, mostly mammalian and microbial, is progressively understood, the complexity of the cellular quality control systems escapes ratio Read More

The technique of combinatorial peptide ligand libraries (CPLL), for capturing and amplifying low-abundance proteins in r-DNA products as well as in a number of other biological systems, is here analyzed in depth and reviewed. This methodology is based on a creation of several millions of bio-specific ligands composed of hexapeptides produced in a combinatorial way. When acting on an overloading and saturation principle, hi Read More

Molecular weight determination of intact recombinant therapeutic proteins is a challenging analytical tool which furnishes valuable information not only for protein structure characterization but also to assess purity and heterogeneity. Up to now several mass spectrometric (MS) approaches have been reported for the measurement of monoisotopic or average masses of intact recombinant therapeutic protein. The choice of Read More

Mass spectrometry is the method of choice for sequencing peptides and proteins and is the preferred choice for characterizing post-translational modifications (PTMs). The most commonly used dissociation method to characterize peptides (i.e. collision-induced dissociation (CID)), however, has some limitations when it comes to analyzing many PTMs. Because CID chemistry is influenced by amino acid side-chains, some modi Read More

Influenza vaccination is recognized as the most effective method for reducing morbidity and mortality due to seasonal influenza. To improve vaccine supply and to increase flexibility in vaccine manufacturing, cell culture-based vaccine production has emerged to overcome limitations of egg-based production. The switch of production system and the need for annual re-evaluation of vaccines for the effectiveness due to fr Read More

Interleukin (IL)-7 is a cytokine inducing the Janus Kinase (JAK)/Signal Transducer and Activator of Transcription (STAT) pathway. As a consequence of IL-7 activating this pathway, STAT5 is phosphorylated. In pharmaceutical quality control, the potency of biopharmaceuticals is commonly assessed by proliferation assays. This is also possible for IL-7 conjugates. However, the disadvantage of these classical “endpoint-assays” is that t Read More

Chronic pain is an unmet medical need. Millions of people suffer from some form of chronic pain that often is co-morbid with cancer, diabetes, arthritis, anxiety and depression: a growing list of diseases that contribute to short/long-term disability and affect quality of life. According to American Pain Foundation, more Americans suffer from some form of chronic pain than diabetes, heart disease, stroke and cancer. Chr Read More

The increasing debate regarding the predictiveness of rodent persistent pain models for clinical efficacy has spurred rapidly evolving numbers and types of novel models from which to choose. While several excellent reviews of these models have been published in recent years, few focus on their specific applications and particular challenges with the use of these models in the setting of drug discovery. Thus, in this review, ho Read More

Osteoarthritis (OA) is a complex disease plagued by a significant unmet need for treatment. To date, no disease- modifying OA drugs (DMOADs) exist and the available symptom-modifying OA drugs (SMOADs) have limitations. Although a complete understanding of the mechanisms of OA pain in humans is lacking, animal models have helped provide insight into the multifaceted origin and manifestation of OA pain. Success in di Read More

Fibromyalgia syndrome (FMS) is a chronic pain syndrome characterized by diffuse musculoskeletal pain. In quantitative sensory testing studies, FMS patients display alterations in heat, cold, and mechanical sensitivity. Genetic studies support a key role for the biogenic amine system, and single nucleotide polymorphisms have been identified in serotonin and dopamine transporter and receptor genes of FMS patients. The pathop Read More

Most cancer patients will experience moderate to severe pain and/or neuropathy during the course of their disease. Recent improvements in the primary treatment of cancer have increased the life span of cancer patients, but not necessarily their quality of life (QoL). The pain and suffering cancer patients experience may be the result of the tumor itself, or the treatments required to arrest tumor growth and progression. In Read More

The need for new pain therapies that provide greater relief without unwanted side-effects drives the search for new drug targets. The identification of endogenous lipid ligands for the two known cannabinoid receptors (CB1 and CB2) has led to numerous studies investigating the role of these endocannabinoids in pain processes. The two most widely studied endocannabinoids are anandamide (AEA; arachidonoyl ethanolamide) Read More

Chronic pain conditions present a huge burden on modern society. Both inflammatory and neuropathic pain are poorly treated in man; the majority of patients do not benefit from adequate pain relief, and side effects of currently used treatments are common. Discovery and development of novel therapies remains an imperative, but the ability to genuinely test the efficacy of novel therapies is often limited by effects at targe Read More

Migraine remains one of the most prevalent and disabling neurological disorders that often affects a person during their most productive years. Migraine afflicts approximately 11% of the adult population globally, causes substantial disability, which translates into lost productivity both at home and at work. Clearly there remains a need for new approaches to treat migraine and calcitonin gene-related peptide (CGRP) rece Read More

The metabotropic glutamate receptors (mGluRs) are expressed pre- and post-synaptically throughout the nervous system where they serve as modulators of synaptic transmission and neuronal excitability. Activation of mGluRs can be pro- or anti-nociceptive, depending on their anatomic location and the signaling cascades to which they couple. Antagonists of Group I mGluRs and agonists of Group II and III mGluRs have sh Read More

Acute pain detection is vital to navigate and survive in one's environment. Protection and preservation occur because primary afferent nociceptors transduce adverse environmental stimuli into electrical impulses that are transmitted to and interpreted within high levels of the central nervous system. Therefore, it is critical that the molecular mechanisms that convert noxious information into neural signals be identified, and the Read More

P2X7 is an ATP-gated non-selective cation channel expressed primarily on cells of hematopoietic origin, such as macrophages and microglia. Since the initial cloning of this channel, enormous progress has been made in the understanding of the physiology, pharmacology and therapeutic utility of P2X7. This article attempts to review the biology of P2X7 with a focus on the complex pharmacology of this channel. Finally, the autho Read More