Pepducins are cell-penetrating
peptides that act as
intracellular
This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...
modulators of signal transference from receptors to
G protein
G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell to its interior. Their a ...
s. Pepducins were first developed at the
Tufts Medical Center
Tufts Medical Center (until 2008 Tufts-New England Medical Center) in Boston, Massachusetts is a downtown Boston hospital midway between Chinatown and the Boston Theater District.
The hospital is a community based medical center for biomedical ...
laboratories of
Dr. Athan Kuliopulos and
Dr. Lidija Covic.
Pepducins employ lipidated fragments of intracellular
G protein-coupled receptor
G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...
loops to modulate GPCR action in targeted
cell-signaling pathways.
A pepducin
molecule
A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioche ...
consists of a short peptide derived from a GPCR intracellular loop tethered to a
hydrophobic
In chemistry, hydrophobicity is the physical property of a molecule that is seemingly repelled from a mass of water (known as a hydrophobe). In contrast, hydrophiles are attracted to water.
Hydrophobic molecules tend to be nonpolar and, t ...
moiety
Moiety may refer to:
Chemistry
* Moiety (chemistry), a part or functional group of a molecule
** Moiety conservation, conservation of a subgroup in a chemical species
Anthropology
* Moiety (kinship), either of two groups into which a society is ...
. This structure allows pepducin
lipopeptide
A lipopeptide is a molecule consisting of a lipid connected to a peptide. They are able to self-assemble into different structures. Many bacteria produced these molecules as a part of their metabolism, especially those of the genus ''Bacillus'', ' ...
s to anchor in the
cell membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
lipid bilayer
The lipid bilayer (or phospholipid bilayer) is a thin polar membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around all cells. The cell membranes of almost all organisms and many vir ...
and target the GPCR/G protein interface via a unique intracellular
allosteric mechanism. Pepducins for over 15 different GPCRs have been successfully produced, several of which have shown activity in preclinical ''
in vivo
Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...
'' models.
An anti-
PAR4 pepducin extended bleeding time in mice and protected against systemic platelet activation and thrombosis.
[
A ]CXCR4
C-X-C chemokine receptor type 4 (CXCR-4) also known as fusin or CD184 (cluster of differentiation 184) is a protein that in humans is encoded by the ''CXCR4'' gene. The protein is a CXC chemokine receptor.
Function
CXCR-4 is an alpha-chemokin ...
agonist pepducin mobilizes bone marrow hematopoietic cells.
References
{{reflist
Lipopeptides