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Arginine-Rich Molecular Transporters for Drugs 159
biological activity, as is the case for amphipathic, antimicrobial peptides. 19,20
Increased flexibility in the backbone or the side chains could allow the guanidine
headgroups to interact more effectively with negative charges on the cell surface.
Using CPK models, increasing the number of methylenes between the arginines not
only allows them to interact with negative charges further apart than homopolymers
of arginine but, interestingly, also permits the guanidines to pack more closely and
interact with putative negative charges that are closely spaced. Further experiments
are needed to distinguish among these possible explanations.
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