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152 Cell-Penetrating Peptides: Processes and Applications
FIGURE 7.5 (Color Figure 7.5 follows p. 14.) A low energy conformation of Ac-R 10-CONH 2.
Ribbon structure showing a representative decamer structure with the 2nd, 5th, and 8th side
chains shown in red. The backbone of the decamer is represented by a green ribbon. Side chains
able to access a common surface (purple) are shown in blue with yellow guanidinium groups.
Mean Fluorescence
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0
0.81
0.01 0.01
0.27
1.03
0.59 0.53
0.74
R A R A R A R R D R D R D R R E R E R E R R F R F R F R R G R G R G R R H R H R H R R I R I R I R R K R K R K R R L R L R L R R M R M R M R RNRRNRRNRR
RPRRPRRPRR
RQRRQRRQRR
RSRRSRRSRR
RTRRTRRTRR
RVRRVRRVRR
RYRRYRRYRR
R7
R10
FIGURE 7.6 Differential cellular uptake of a set of decamers with each of the naturally
occurring amino acids substituted in positions 2, 5, and 8 compared with R7 and R10. The
mean fluorescence from 5000 cells of a human T cell line, Jurkat, is shown after incubation
with 25 µM of each of the peptides for 5 min. Uptake was measured in triplicate at concentrations
varying from 400 nM to 50 µM. Data are shown at a single concentration for ease of
presentation; details of the assay are described in Section 7.2.
have established that the guanidine headgroup of arginine can form intramolecular
salt bridges with either phosphate or carboxylate functionalities, and in so doing
reduce the number of guanidines available for interaction with the cell surface
(unpublished results). A similar effect could explain the relatively inefficient ability
0.45
1.02
0.47 0.49 0.40
0.86
0.95
0.77
0.20
0.11
1.00