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Anti-Inflammatory
& Anti-Allergy Agents in Medicinal Chemistry
ISSN: 1871-5230
Anti-Inflammatory & Anti-Allergy
Agents in Medicinal Chemistry
Volume 7, Number 4, December 2008
Contents
Mimetic Peptides in Allergy and Inflammation
Treatment
Guest Editor: Demitrios H. Vynios
Editorial Pp. 239
Biodegradable Polymer Based Particulate Carrier(s)
for the Delivery of Proteins and Peptides Pp. 240-251
Neeraj Mishra, Amit K. Goyal, Kapil Khatri, Bhuvaneshwar
Vaidya, Rishi Paliwal, Shivani Rai, Abhinav Mehta, Shailja
Tiwari, Shiva Vyas and Suresh P. Vyas
[Abstract] [Full
text article]
IgE-Mediated Disorders: Current Therapeutics and
New Strategies Involving Synthetic Peptides Pp.
252-263
Antonio Verdoliva and Maria Rossi
[Abstract] [Full
text article]
Allergen-Induced Inflammation Pp.
264-280
Ronald Mathison, Katherine Morris, Joseph
S. Davison and Dean Befus
[Abstract] [Full
text article]
Derivatives of IL-16 to Modulate Airway Inflammation
Pp. 281-293
Sophie Laberge and William W. Cruikshank
[Abstract] [Full
text article]
Peptides as Therapeutic Agents or Drug Leads for
Autoimmune, Hormone Dependent and Cardiovascular Diseases
Pp. 294-306
Efthimia Mantzourani, Despoina Laimou, Minos
Timotheos Matsoukas and Theodore Tselios
[Abstract] [Full
text article]
Abstracts
[Back to top]
Editorial :
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 25% 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 de-livery 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 col-laboration 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.
Demitrios H. Vynios, Ph.D.
Guest Editor
Anti-Inflammatory & Anti-Allergy Agents in Medicinal
Chemistry
Professor of Connective Tissue Biochemistry
Laboratory of Biochemistry, Department of Chemistry
University of Patras
265 00 Patras
Greece
[Back to top] [Full
text article]
Biodegradable Polymer Based Particulate Carrier(s)
for the Delivery of Proteins and Peptides
Neeraj Mishra, Amit K. Goyal, Kapil Khatri, Bhuvaneshwar
Vaidya, Rishi Paliwal, Shivani Rai, Abhinav Mehta, Shailja
Tiwari, Shiva Vyas and Suresh P. Vyas
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.
[Back to top]
[Full
text article]
IgE-Mediated Disorders: Current Therapeutics and New
Strategies Involving Synthetic Peptides
Antonio Verdoliva and Maria Rossi
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 (FcεRI)
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-FcεRIantibodies,
or chimeric proteins targeting Fc receptors. Nevertheless,
validation of IgE and FcεRI
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/FcεRI
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 (β-hexosaminidase
release) and in vivo (passive and active cutaneous
anaphylaxis) models of allergy, without interfering with IgE/FcεRI
or IgE/Ag interaction, thus opening the way to development
of new antiallergic drugs.
[Back to top]
[Full
text article]
Allergen-Induced Inflammation
Ronald Mathison, Katherine Morris, Joseph
S. Davison and Dean Befus
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 (β2-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
out-comes. 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.
[Back to top] [Full
text article]
Derivatives of IL-16 to Modulate Airway Inflammation
Sophie Laberge and William W. Cruikshank
The full devel opment 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 TH2
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 TH2 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.
[Back to top]
[Full
text article]
Peptides as Therapeutic Agents or Drug Leads for Autoimmune,
Hormone Dependent and Cardiovascular Diseases
Efthimia Mantzourani, Despoina Laimou, Minos
Timotheos Matsoukas and Theodore Tselios
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.
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