Scientists at the CNRS "Laboratoire des aminoacides, peptides
et protéines" (LAPP, Amino Acids, Peptides and Proteins
Laboratory) are studying bradykinin, a peptide hormone found in mammals.
Peptides are natural molecules present in all living organisms which
play an essential role in many biological functions. Bradykinin is
involved in many physiological and physiopathological processes such
as pain, allergies, chronic and acute inflammation and some cardiovascular
diseases.
The
team is unraveling the bradykinin's action mechanisms and defining
the chemical elements essential to its interaction with receptors.
They have designed molecules that can interact with the hormone receptors
but which block (antagonist) or amplify (agonist) the biological response.
These molecules may help in defining the role of hormones in general
and bradykinin in particular in certain physiological or pathological
processes.
These
molecules may be used for drug design: a bradykinin antagonist, for
example, may relieve pain, allergies, low blood pressure, or even
cranial trauma. An agonist may be used as an adjuvant for cancer treatment
to increase the permeability of the hemato-encephalic barrier to the
anti-cancer drugs.
The
team has focused its research on the design of bradykinin antagonists
that can be taken orally, and to the development of powerful agonists.
However, the use of peptides in medicine is associated with low bioavailability,
so the peptides have to be converted into non-peptide type molecules
without loss of activity.
Modifying
the bradykinin sequence has enabled bradykinin antagonists and agonists
to be designed in such a way as to gradually reduce their peptide
nature. These compounds constitute important pharmacological tools
for evaluating the role of bradykinin in physiological processes and
some diseases and may pave the way for new "drugs."
