Helical peptide–polyamine and –polyether conjugates as synthetic ionophores

Following the analysis proposed by Regen,8,9 its key functional elements are i) the long and rigid hydrophobic steroid nucleus; ii) the flexible hydrophilic spermidine chain terminating with a positively charged amino group; iii) the anionic polar head group

Monica Benincasa

2015

Scholarcy highlights

  • Common feature found in several natural ionophores is the presence of a lipophilic, usually rigid, backbone connected to a hydrophilic subunit
  • The inability to transport Na+ associated with potent pH discharge activity suggests that 1a forms anion selective pores in which the transport of H+ is counterbalanced by the transport of chloride in analogy with the anion selective transport mechanism described for squalamine mimics bearing polyamine chains.19a,22 In any case, control experiments with the relatively large calcein dye indicate that, whatever the mechanism, the membrane defects formed by conjugates 1 are not large enough to allow the transport of calcein and that the ionophores are not able to cause lysis of the liposomes
  • We have reported a new approach to the design of synthetic ionophoric molecules using a helical peptide as a rigid lipophilic moiety
  • A direct correlation between ionophoric activity in model membranes and biological activity is complex to demonstrate,23 the ability of 1a to permeabilize the bacterial membranes suggests that ion transport might play a significant role in the mechanism of action of this compound in cells
  • Studies are in progress to evaluate these possibilities and to better define the mechanism of action of this new class of biological active synthetic ionophores

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