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1) Peptide phage display: isolate binders of semiconductors
Phage structure and phage display selection process. (a) Schematic diagram of phage and its genome and (b) phage-display process to identify specific binding peptide motifs against desired targets.
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2) Use the isolated phages as nucleation centers for the fabrication of nanoparticles and nanowires
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Phages as vehicles for gene and vaccine delivery
Application of filamentous phagesAs nanomedicines
Phages as tool for imaging
Phages as vehicles for gene and drug delivery
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Components of a targeted drug carrying platform
Drug
DrugTargeting
moiety
Specificity
Affinity
Chemical tolerance
Drug Carrier
High capacitybiocompatibility
Labile linker
Proper kineticsTemporalSpatial
Potency
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The filamentous bacteriophageas a targeted drug-carrying nanomedicine
-g3 protein
- g6 protein -g8 protein
-g9 protein
- g7 protein
XII
I
g3
g8
g5
g2
g10
IG
g4
g1
g9
g6
800-2000 nm (dependent on the size of the packaged genome)
6nm
Scheme of the filamentous Fd phage. In out system, the minor coat protein, p3 (g3p) carries the targeting moiety which the drug, and the engineered release mechanism are on p8 (g8p).
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IgG complexed to fUSE5-ZZ phage through a p3-displayed ZZ domain
- IgG
- ZZ domain
0
10
20
30
40
50
60
70
80
90
100
110
0.01 0.10 1.00 10.00 100.00 1000.00competing human IgG (μg/ml)
% o
f m
axim
al s
ign
al
*3 dil *9 dil
fUSE5-ZZ phage used for targeting. A Scheme of the filamentous fUSE5-ZZ phage. B. Evaluationof ZZ domain display by an immunoblot. Phage particles (each lane is identified with the corresponding phage name below it)were separated by SDS/PAGE and electro-botted onto nitrocellulose, and the p3 minor coat protein or the derived ZZ domain-p3 fused derivative was detected with an anti-p3 antibody. The upper arrow marks the position of the ZZ-p3 fusion, while the lower arrow marks the position of the wild-type p3 coat protein. C. Evaluation of antibody binding capacity by competitive ELISA. 10 12 fUSE5-ZZ phages were complexed with 0.6 g (*3 dil) or 0.2 g (*9 dil) of HRP-conjugated rabbit anti mouse IgG as tracer, in the presence of varying concentrations of protein-A purified human IgG. The residual HRP on the phages was detected using the substrate TMB.
M13
KO
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pCA
NT
AB
5-Z
ZfUSE
5 -
ZZ
A B
C
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Preparation of drug-linker adductChloramphenicol was modified in two steps to create an ester bond between CAMand a linker (originated in glutatic anhydride) The linker CAM complex is activated for lysine conjugation by the NHS procedure.
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Partial growth inhibition of staphylococcus aureusby antibody-targeted drug-carrying phages (3000 Cam/phage)
Similar Partial growth inhibition was obtainedby peptide-targeted phages