2.3 Conclusion
45
ER-1a
ER-1b
DAPI
FITC
Merge
a)
PDI-1b
PDI-1a
PDI-1b
b)
c)
FITC
20um
4 ° C
NaN 3 +2-Deoxyglucose
Merge
Fig. 2.16 (A) Fluorescent confocal microscopy images of MCF-7 cells incubated with FITClabeled peptides ER-1a/1b (5 μM) at 37°C. (B–D) Flow cytometry measurements of MCF-7 cells
treated with ER-1a/1b, PDI-1a/1b, and PDI-2a/2b (5 μM) at 37°C
Moreover, this concept was translated into constructing MDM2 and ERα peptide
ligands, which show excellent α-helicity nucleation properties and dramatically
enhanced binding affinities. More importantly, the significant differences in the
permeability of the long peptide diastereomers clearly indicate the importance of
increasing peptide helicity in the construction of constrained peptides. We unambiguously demonstrated that increasing the helicity of a constrained peptide could
increase its permeability. In addition, the influence of the substitution groups at the
chiral center on the peptides’ binding affinity suggests that this chiral center could
be utilized as an additional modification site away from the peptide backbone that
45
ER-1a
ER-1b
DAPI
FITC
Merge
a)
PDI-1b
PDI-1a
PDI-1b
b)
c)
FITC
20um
4 ° C
NaN 3 +2-Deoxyglucose
Merge
Fig. 2.16 (A) Fluorescent confocal microscopy images of MCF-7 cells incubated with FITClabeled peptides ER-1a/1b (5 μM) at 37°C. (B–D) Flow cytometry measurements of MCF-7 cells
treated with ER-1a/1b, PDI-1a/1b, and PDI-2a/2b (5 μM) at 37°C
Moreover, this concept was translated into constructing MDM2 and ERα peptide
ligands, which show excellent α-helicity nucleation properties and dramatically
enhanced binding affinities. More importantly, the significant differences in the
permeability of the long peptide diastereomers clearly indicate the importance of
increasing peptide helicity in the construction of constrained peptides. We unambiguously demonstrated that increasing the helicity of a constrained peptide could
increase its permeability. In addition, the influence of the substitution groups at the
chiral center on the peptides’ binding affinity suggests that this chiral center could
be utilized as an additional modification site away from the peptide backbone that