Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (v.7, #4)

Allergy can be defined as an adverse immune-mediated overreaction to otherwise innocuous environmental substances, that is, allergens. It is well established that allergic diseases (atopic diseases), such as hay fever, rhinoconjunctivitis, allergic bronchial asthma, allergic dermatitis, eczema, urticaria, angioedema and anaphylaxis, are global health problems affecting more than 25and#x25; of the worldwide population. Allergic disorders remain the most common cause of chronic ill health and socioeconomic burden for health-related quality of life and healthcare costs. Treatment of allergy may be proceeded by using drugs such as antihistamines and topical corticosteroids to eliminate symptoms or suppress allergic inflammation without addressing the underlying cause, or by using more or less sophisticated therapies that target specific cells or macromolecules. Among the targeted therapies, those using peptide drugs are highly promising, since peptides have cheap production, various ways of delivery and low side-effects. Recent researh is focused on the characterization of new allegrens, the detailed mechanism of allergic reaction, and the prevention or the treatment of allergic reaction in patients. This special issue of Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry is dedicated to Mimetic peptides in allergy and inflammation treatment. Emphasis has given in the recent developments in allergy basic knowledge and the new pharmacotherapies employed for its treatment. I wish to thank all the authors of the publications for their readiness and cooperation in this issue, which we hope will have a strong impact in the area of Mimetic peptides in allergy and inflammation treatment. I would also like to thank the Editor-In- Chief, Dr. Bahar Tunctan, for her willingness to entrust me with the preparation of this special issue and for her unlimited collaboration in all steps necessary. From my personal point of vantage, I am thankfull and consider myself to have been rewarded for extending my knowledge on this field during the process of reading and editing the articles.

Biodegradable Polymer Based Particulate Carrier(s) for the Delivery of Proteins and Peptides by Neeraj Mishra, Amit Goyal, Kapil Khatri, Bhuvaneshwar Vaidya, Rishi Paliwal, Shivani Rai, Abhinav Mehta, Shailja Tiwari, Shiva Vyas, Suresh Vyas (240-251).
Construction of safe and effective delivery systems for proteins and peptides is demand of current clinical practices. Biodegradable polymers based particulates carriers fulfill much of the requirement in this applicable field. Number of marketed products related to biodegradable polymers encapsulating proteins is increasing. However, it has not achieved its proper place since problems related to the protein processing and stabilization limits the scientific community. In this present review we have summarized various aspects related to the formulation and processing of biodegradable polymerized microparticles/ nanoparticles for delivery of therapeutic proteins and peptides. A brief introduction of biodegradable polymers has been incorporated for reader's benefit. In addition, biodegradable polymers based carriers designed for vaccine delivery has been incorporated in detail. Functionalized biodegradable carrier(s) for site specific delivery of proteineous matter has also been discussed.

Most of the current therapies for the treatment of atopic diseases are based on drugs that inhibit or suppress components of the allergic inflammatory response. Antihistamines, bronchodilators, antiallergic drugs and corticosteroids remain by far the most effective therapeutic response to allergic diseases in reducing symptoms and concomitant inflammatory reactions. The last two decades witnessed a large number of works aimed at identifying medications targeting specific steps in the allergic cascade. Because the binding of IgE to mast cells via the high affinity surface mast cell receptor (Fcand#949;RI) is the central event in allergic manifestations, its inhibition seems the best approach for designing innovative antiallergic drugs. Progress has been made on the molecular level by using anti-IgE and anti-Fcand#949;RI antibodies, or chimeric proteins targeting Fc receptors. Nevertheless, validation of IgE and Fcand#949;RI as crucial targets for allergic disorders is provided by a wealth of studies where the antiallergic activity of small molecules, such as peptides, able to inhibit IgE/Fcand#949;RI interaction, was assessed. D-PAM, a tetrameric IgE-binding tripeptide, derived through combinatorial chemistry, represents a new and innovative mechanism for atopy treatment. Due to its polycationic structure, this peptide is active in in vitro (and#946;- hexosaminidase release) and in vivo (passive and active cutaneous anaphylaxis) models of allergy, without interfering with IgE/Fcand#949;RI or IgE/Ag interaction, thus opening the way to development of new antiallergic drugs.

Allergen-Induced Inflammation by Ronald Mathison, Katherine Morris, Joseph Davison, Dean Befus (264-280).
Allergen-induced inflammation manifests as allergic asthma, dermatitis, rhinitis, conjunctivitis, food allergies, and life- threatening anaphylaxis. Allergic reactions consist of an acute phase hypersensitivity reaction and late phase inflammation. Current therapeutic strategies consist of immunotherapy to induce tolerance to an allergen or pharmacotherapy to treat either the acute phase reaction or the chronic inflammation associated with allergic disease. For bronchial asthma, the allergic disease with the greatest worldwide burden, three medications (and#946;2-adrenoceptor agonists, glucocorticoids and leukotriene antagonists) are the mainstays of therapy, which when used alone or in combination control asthma symptoms in many asthmatics. A recent anti-IgE therapy has benefited some difficult to manage patients, however a significant proportion of asthma patients do not respond well to currently available drugs. There is a need for new effective lost-cost therapies for asthma and other allergic diseases to complement existing therapies and improve long-term outcomes. There are several potential therapeutic targets including transcription factors, cytokines, chemokines and their receptors, proteases, and cell adhesion molecules. Within the next generation of anti-allergy drugs one or more will probably be a peptide or a peptide mimetic.

Derivatives of IL-16 to Modulate Airway Inflammation by Sophie Laberge, William Cruikshank (281-293).
The full development of allergic airway responses in asthma is critically dependent on CD4+ T cells. Through interaction with CD4 molecule, IL-16 acts specifically on CD4+ cells. In vitro, IL-16 has been characterized as a chemoattractant for CD4+ immune cells and as a regulator of T cell functions inhibiting T cell receptor-mediated activation, an effect that is more predominant in T 2 cells. IL-16/CD4 interaction also regulates chemokine receptor signaling. The contribution of IL-16 in allergic airway inflammation has been studied both in humans and in animal models of asthma. Airway expression of IL-16 is upregulated in patients with ongoing asthma and in experimental models of allergic airway inflammation. The immunomodulatory function of IL-16 has been demonstrated in murine models of asthma in which systemic treatment with IL-16 inhibits antigen-induced airway responses and T 2 T cell cytokine production. This review addresses the current data regarding IL-16 protein and gene structure; the interaction of IL-16 with CD4; the biological activities of IL-16; its immunoregulatory role in allergic airway inflammation. In addition, we discuss the known and potential therapeutic applications for IL-16 and IL-16 peptide derivatives in allergic airway inflammation.

Peptides as Therapeutic Agents or Drug Leads for Autoimmune, Hormone Dependent and Cardiovascular Diseases by Efthimia Mantzourani, Despoina Laimou, Minos Matsoukas, Theodore Tselios (294-306).
Peptides regulate most physiological processes, mainly by binding to specific receptors located on the cell surface and inducing a series of signals, neurotransmissions or the release of growth factors. There has been a rapid expansion in the use of peptides as therapeutic agents after the 1960s, but a series of unfortunate side effects present in Phase I and II clinical studies combined with their low bioavailability, led to the introduction of the idea of peptidomimetics as alternative compounds that mimic the biological activity of peptides, while offering the advantages of increased bioavailability, biostability, bioefficiency, and bioselectivity. Since then new peptides with promising in vitro results, involving the monoclonal antibody expansion, as well as the newly launched research field for novel formulations for increasing peptides' bioavailability, redirected the interest on the peptide market. In this report we will highlight three areas where the use of peptides has shown promising results, with products that are either currently used as drugs or included into Phase III clinical studies.