Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.10.1 (
ERK
)
95,504
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The synthesis and
in vitro
evaluation of four mesoporphyrin IX-peptide conjugates designed to target
EGFR
, over-expressed in colorectal and other cancers, are reported. Two peptides with known affinity for
EGFR
, LARLLT (
1
) and GYHWYGYTPQNVI (
2
), were conjugated to mesoporphyrin IX (
MPIX
,
3
)
via
one or both the propionic side chains, directly (
4
,
5
) or with a triethylene glycol spacer (
7
,
8
). The conjugates were characterized using NMR, MS, CD, SPR, UV-vis and fluorescence spectroscopies. Energy minimization and molecular dynamics suggest different conformations for the conjugates. SPR studies show that conjugate
4
, bearing two LARLLT with no PEG spacers, has the greatest affinity for binding to
EGFR
, followed by conjugate
7
with two PEG and two LARLLT sequences. Molecular modeling and docking studies suggest that both conjugates
4
and
7
can bind to monomer and dimer
EGFR
in open and closed conformations. The cytotoxicity and cellular targeting ability of the conjugates were investigated in human HEp2 cells over-expressing
EGFR
. All conjugates showed low dark- and photo-toxicities. The cellular uptake was highest for conjugates
4
and
8
and lowest for
7
bearing two LARLLT linked
via
PEG groups, likely due to decreased hydrophobicity. Among the conjugates investigated
4
is the most efficient
EGFR
-targeting agent, and therefore the most promising for the detection of cancers that over-express
EGFR
.
...
PMID:Targeting of the epidermal growth factor receptor with mesoporphyrin IX-peptide conjugates. 2773 94
