Amphipathic short helix-stabilized peptides with cell-membrane penetrating ability.

ABSTRACT

We synthesized four types of arginine-based amphipathic nonapeptides, including two homochiral peptides, R-(L-Arg-L-Arg-Aib)3-NH2 (R=6-FAM-ß-Ala FAM-1; R=Ac Ac-1) and R-(D-Arg-D-Arg-Aib)3-NH2 (R=6-FAM-ß-Ala ent-FAM-1; R=Ac ent-Ac-1); a heterochiral peptide, R-(L-Arg-D-Arg-Aib)3-NH2 (R=6-FAM-ß-Ala FAM-2; R=Ac Ac-2); and a racemic mixture of diastereomeric peptides, R-(rac-Arg-rac-Arg-Aib)3-NH2 (R=6-FAM-ß-Ala FAM-3; R=Ac Ac-3), and then investigated the relationship between their secondary structures and their ability to pass through cell membranes. Peptides 1 and ent-1 formed stable one-handed α-helical structures and were more effective at penetrating HeLa cells than the non-helical peptides 2 and 3.