Dr.
Jorg Stetefeld has developed a novel way to deliver small molecule drugs within
a protein “cage”. This may be used to:
·
Deliver
relatively insoluble drugs.
·
It
may be used to alter drug release, absorption, distribution, metabolism and
elimination.
·
The
technology also provides a method to produce bio-engineered targeted ligands to
deliver molecules to specific cell types.
The
Stetefeld Drug Delivery Matrix:
Cartilage
oligomeric matrix protein (COMP) is a non-collagen glycoprotein found in the
connective tussue. It is a homopentamer consisting of five subunits held
together by interchain disulfide bridges.
Dr.
Stetefled has elucidated the crystal structure of the recombinant coiled-coil
domain of COMP (COMPcc) revealed a 73Å-long axial pore with a diameter of 2–6Å.
This pore, outlined in yellow at right, is divided into two hydrophobic cavities
by a ring of conserved glutamines which form a network of hydrogen bonds.
Crystal
structures of the binding properties of drugs (see right), including
5-Fluorouracil within the hydrophobic channel (the channel can expand to fit
some ligands: a “breathing effect”) demonstrate that COMPcc may be used as a
storage and delivery system for charged and hydrophobic compounds.
Fluorescent
labeling demonstrates the cell-surface binding and subsequent cellular uptake of
the delivery construct (top). The monomer units are produced by recombinant
protein expression and protein ligand moieties may readily be incorporated in
order to target the unit to cells.