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Robin B. Goldsmith
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# 052694
Scripps ScientistsPresentStrategy for the Designof PeptideNanotubeswith
Implications for New Anticancer Agents, Antibiotics
La Jolla, CA. May 26, 1994- A rapid, simple,and versatilemethodfor building minute
holes-nanotubes-in cell membraneshasbeendevelopedby investigatorsat The Scripps
ResearchInstitutein La Jolla, California. The work has implicationsfor the designof
novel anticanceragentsand antibioticsas well as new waysto infusedrugs and even
moleculesas large as genesinto cells.
The work was reportedin today's (May 26) issueof the journal Nature in an article,
Artificial Transmembrane
Ion ChannelsFrom Self-Assembling
PeptideNanotubes,by Drs.
M. RezaGhadiri, JuanR. Granja,and LukasK. Buehlerin the Departmentsof Chemistry,
Molecular Biology, and Cell Biology at Scripps.
The strategythey developedis a simpleone. In earlier studies,they had shownthat rings
madeof alternatingD- and L-amino acidswould, underappropriateconditions,selfassembleinto stacksto form a tube, much like a roll of Life Savers.Moreover, they found
that this self-assembly
would occur no matterwhich aminoacidsthey usedto makethe
componentrings, and that they could dictate the diameterof the tubessimply by making
the rings larger or smaller.
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Nanotubes
Accordingly, they preparedrings comprisedof hydrophobicamino acidsthat would
dissolvein lipids but not in water. Next, they introducedthe rings into the membraneof
lipid vesicles,structuresnot unlike minute soapbubbles,and showedthat the rings selfassembledto form tubesthroughthe membrane.They then showedthat thesetubeswere
highly efficient conduitsfor the passageof saltsand hydrogenions throughthe vesicle
membranes.
Virtually all cells maintainan internalpH and concentrationof saltsand other ions that is
often quite different than the externalenvironment.This imbalanceis regulatedby proteins
that form channelsthrough the membranethat permit the passageof small moleculesin
and out as needed.
When the imbalanceis upsetor eliminated,cells die. Thereare somenaturalantibiotics
that kill cells by building holes through the membranesof bacteriaand other
microorganismsthat allow the internal pH and ionic strengthto maintain equilibrium with
the outsideof the cell.
According to Ghadiri, "'Wethink thesenanotubesmight do preciselythe samething. We
have comparedour nanotubeswith theseantibiotics and find that they are even more
efficient in allowing the passageof ions throughmembranes.Thus, nanotubescould be
usedas antibiotics,with the advantagethat sincewe can alter their chemicalmakeupat
will, it might be possibleto targetthemmore selectivelyagainstcertainpathogensand
perhapsevencancercells."
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Nanotubes
Another possibility would be the introduction of geneticmaterial into cells for gene
therapy.At present,geffingDNA or RNA into cells is a major problem. Using virusesfor
this purposewill work, but the virusesthemselvesare problematic. However, with a low
concentrationof large rings, a small numberof relatively large pores could be introduced
into the cell membrane,pores large enoughto permit the passageof large molecules.
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