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Interactions of Cell-Penetrating Peptides with Membranes 165
Most data available up to now are related to the two first steps, while those related
to the third are more perspective-relevant.
8.2 STRUCTURAL DETERMINATIONS
Although much progress has been made recently in identification of peptide conformations
in the presence of membranes or membrane mimicking media, determination of
peptide structures in membranes remains a difficult task. This obligatory step for understanding
the membrane crossing process requires conformational studies together with
analysis of peptide–phospholipid interactions and their structural consequences.
We present here the most useful methods to be used for these two types of
investigations and also point out their limits and the pertinence of their information.
Two families of peptides will be used to illustrate the various information that can
be obtained by the different techniques used in such situations. The first peptide
family is composed of primary amphipathic peptides based on the association of a
cationic nuclear localization sequence (NLS) 43 with either a signal peptide (SP) 44 or
a sequence issued from a fusion peptide (FP). 45
TABLE 8.1
Sequences of the Peptides of the SP–NLS Series
M-G-L-G-L-H-L-L-V-L-A-A-A-L-Q-G-A-W-S-Q-P-K-K-K-R-K-V [1]
M-G-L-G-L-H-L-L-V-L-A-A-A-L-Q-G-A---------K-K-K-R-K-V [2]
TABLE 8.2
Sequences of the Peptides of the FP–NLS Series and Related Peptides
G-A-L-F-L-G-W-L-G-A-A-G-S-T-M-G-A-W-S-Q-P-K-K-K-R-K-V [3]
G-A-L-F-L-G-W-L-G-A-A-G-S-T-M-G-A----R----K-K-K-R-K-V [4]
G-A-L-F-L-G-F-L-G-A-A-G-S-T-M-G-A-W-S-Q-P-K-S-K-R-K-V [5]
G-A-L-F-L-A-F-L-A-A-A-L-S-L-M-G-L-W-S-Q-P-K-K-K-R-K-V [6]
Both these series are composed of primary amphipathic peptides for which no
folding is required for presenting the amphipathic character.
TABLE 8.3
Examples of Peptides Belonging to the Family of Secondary
Amphipathic Peptides
K-L-A-L-K-L-A-L-K-A-L-K-A-A-L-K-L-A from [31]
L-A-R-L-L-A-R-L-L-A-R-L-L-R-A-L-L-R-A-L-L-R-A-L from [34]
For these two peptides folding into an α-helical form is required for presenting
the amphipathic character.