Influence of stearyl and trifluoromethylquinoline modifications of the cell penetrating peptide TP10 on its interaction with a lipid membrane

7
The PepFect family of cell-penetrating peptides (CPPs) was designed to improve the delivery of nucleic acids across plasma membranes. We present here a comparative study of two members of the family, PepFect3 (PF3) and PepFect6 (PF6), together with their parental CPP transportan-10 (TP10), and their interactions with lipid membranes. We show that the addition of a stearyl moiety to TP10 increases the amphipathicity of these molecules and their ability to insert into a lipid monolayer composed of zwitterionic phospholipids. The addition of negatively charged phospholipids into the monolayer results in decreased binding and insertion of the stearylated peptides, indicating modification in the balance of hydrophobic versus electrostatic interactions of peptides with lipid bilayer, thus revealing some clues for the selective interaction of these CPPs with different lipids. The trifluoromethylquinoline moieties, in PF6 make no significant contribution to membrane binding and insertion. TP10 actively introduces pores into the bilayers of large and giant unilamellar vesicles, while PF3 and PF6 do so only at higher concentrations. This is consistent with the lower toxicity of PR and PF6 observed in previous studies.

Majhenc, Janja (författare)
Kogej, Ksenija (författare)
Sillard, RannardStockholms universitet,Institutionen för neurokemi (författare)
Langel, ÜloStockholms universitet,Institutionen för neurokemi(Swepub:su)ulo (författare)
Anderluh, Gregor (författare)
Zorko, Matjaz (författare)
Stockholms universitetInstitutionen för neurokemi (creator_code:org_t)

Ingår i:Biochimica et Biophysica Acta - Biomembranes: Elsevier BV1818:3, s. 915-9240005-27361879-2642

Av författaren/redakt...: Anko, Maja; Majhenc, Janja; Kogej, Ksenija; Sillard, Rannard; Langel, Ülo; Anderluh, Gregor; visa fler...; Zorko, Matjaz; visa färre...

Om ämnet

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.