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Mini-Reviews
in Medicinal Chemistry
ISSN: 1389-5575
OPEN ACCESS PLUS
Contents
The AMP-Activated Protein Kinase: Role in Regulation of Skeletal
Muscle Metabolism and Insulin Sensitivity, 2007,
7, 521-528
Gregory R. Steinberg and Sebastian Beck Jørgensen
[Abstract] [Full
text article]
Quantum Chemical Analysis of MHC-Peptide
Interactions for Vaccine Design, 2010, 10, 746-758
W.A. Agudelo and M.E. Patarroyo
[Abstract] [Full
text article]
Abstracts
[Back to top]
The AMP-Activated Protein Kinase: Role in Regulation
of Skeletal Muscle Metabolism and Insulin Sensitivity
Gregory R. Steinberg and Sebastian Beck Jørgensen
[Full
text article]
Over the past decade, an epidemic of obesity has developed
throughout the Western World. In recent years, significant
interest has focused on the role of the AMP-activated protein
kinase (AMPK) as a potential therapeutic target for the treatment
of obesity and type 2 diabetes and is such the focus of this
review. Specifically, the potential role of AMPK in skeletal
muscle metabolism as it relates to the insulin sensitizing
effects of exercise and the hormones, leptin, adiponectin,
ciliary neurotrophic factor and interleukin-6 are discussed.
We caution that despite the convincing associations between
the activation of AMPK signalling and the restoration of insulin
sensitivity, future studies in genetic models of AMPK deficiency
or constitutive activation within skeletal muscle are needed
to evaluate the quantitative role of AMPK and to validate
whether strategies designed to activate skeletal muscle AMPK
may be important for regulating whole-body insulin sensitivity.
[Back to top]
Quantum Chemical Analysis of MHC-Peptide Interactions for
Vaccine Design
W.A. Agudelo and M.E. Patarroyo
[Full
text article]
The development of an adequate immune response against pathogens
is mediated by molecular interactions between different cell
types. Among them, binding of antigenic peptides to the Major
Histocompatibility Complex (MHC) molecule expressed on the
membrane of antigen presenting cells (APCs), and their subsequent
recognition by the T cell receptor have been demonstrated
to be crucial for developing an adequate immune response.
The present review compiles computational quantum chemistry
studies about the electrostatic potential variations induced
on the MHC binding region by peptide’s amino acids,
carried out with the aim of describing MHC–peptide binding
interactions. The global idea is that the electrostatic potential
can be represented in terms of a series expansion (charge,
dipole, quadrupole, hexadecapole, etc.) whose three first
terms provide a good local approximation to the molecular
electrostatic ‘landscape’ and to the variations
induced on such landscape by targeted modifications on the
residues of the antigenic peptide. Studies carried out in
four MHC class II human allele molecules, which are the most
representative alleles of their corresponding haplotypes,
showed that each of these molecules have conserved as well
as specific electrostatic characteristics, which can be correlated
at a good extent with the peptide binding profiles reported
experimentally for these molecules. The information provided
by such characteristics would help increase our knowledge
about antigen binding and presentation, and could ultimately
contribute to developing a logical and rational methodology
for designing chemically synthesized, multiantigenic, subunit-based
vaccines, through the application of quantum chemistry methods.
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