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Squalamine is not a proton ionophore
B S Selinsky1, R Smith, A Frangiosi
1Department of Chemistry, Villanova University, Villanova, PA 19085, USA. selinsky@chem.vill.edu
Biochimica Et Biophysica Acta
|March 8, 2000
Summary
Squalamine does not transport ions across phospholipid membranes, unlike a similar synthetic analog. This suggests diverse antimicrobial mechanisms for aminosterols, potentially unrelated to ion transport.
Area of Science:
- Biochemistry
- Membrane Biophysics
- Antimicrobial Agents
Background:
- Squalamine, an aminosterol antibiotic from dogfish sharks, causes membrane defects allowing molecule translocation.
- A structurally similar synthetic aminosterol acts as a proton ionophore without gross membrane disruption.
Purpose of the Study:
- To investigate the ionophoric activity of squalamine in anionic and zwitterionic phospholipid vesicles.
- To compare the membrane interaction and activity of squalamine with its synthetic analog.
Main Methods:
- Testing squalamine's ionophoric activity in phosphatidylglycerol (PG) and phosphatidylcholine (PC) vesicles.
- Utilizing radiolabeled squalamine to track its incorporation into vesicles.
- Synthesizing and testing a novel aminosterol analog for ionophoric and lytic activity.
Main Results:
- Squalamine exhibited no ionophoric activity in PG, PC, or mixed lipid vesicles.
- Radiolabeled squalamine fully associated with PG vesicles, while half incorporated into PC vesicles.
- The synthetic analog showed ionophoric activity in PG vesicles but lacked lytic activity.
Conclusions:
- Squalamine's antimicrobial activity may not involve ion transport across membranes.
- The findings suggest multiple mechanisms for aminosterol antimicrobial action, possibly structure-dependent.
- An alternative, common antimicrobial mechanism for aminosterols may exist independently of ionophoric properties.