Biomedical Engineering Reference
In-Depth Information
explained by the fact that these fusion proteins would not be
retained on the culture plates for long periods; thus, their e
-
cacy is not persistent. An improved cell-binding EGF (containing
an RGD sequence) was generated recently via the incorporation of
hydrophobic linkersequences
40
and collagen-bindingsequences.
41
Van Lonkhyzen
et al
.
42
produced a chimeric protein of IGF-I and
vitronectin. This protein (VN:IGF-I) associates with IGF-I-binding
protein (IGF-BP). The complex of VN:IGF-I and IGF-BP binds to both
theIGF-Ireceptorandtointegrin(thusbindstocells)andstimulates
receptor-mediated and integrin-mediated pathways. As a result, the
VN:IGF-I/IGF-BPcomplexexhibitsahighercellproliferationactivity
compared with the IGF-I/IGF-BP complex.
17.3.4
Other Binding Growth Factors
Growth factors were also engineered to bind to artificial materi-
als. BMP2 was fused with a polypeptide sequence that has a
n-
ity to titanium
43
; the peptide sequences were selected with a gene
evolution approach using a phage display system. The fusion of this
sequence allows the reversible binding of BMP2 to titanium, with
retention of itsbiologicalactivity.
Ogiwara
et al
.
44
producedanEGFfusionproteincoupledwiththe
Fc region of immunoglobulin G (IgG). The Fc region is often used
as a fusion tag to allow extracellular domains of large membrane
proteins or receptor molecules to adhere nonspecifically to solid
surfaces. These authors used the hydrophobicity of the Fc region
as a binding domain for hydrophobic artificial substrates, although
this type of fusion protein is not considered as a binding growth
factor.
Dohney
et al
.
45
fused the cellulose-binding domain of bacterial
xylanase with the extracellular domain of the stem cell factor (SCF).
The fusion construct binds to cellulose tightly and stimulates the
proliferation ofSCF-dependent murine andhuman cells.
17.4 Application of Engineered Binding Growth Factors
The binding growth factors were designed to continue to stimu-
late signaling for a long time, like chemically immobilized growth
Search WWH ::
Custom Search