Secondary conformation of short lysine‐ and leucine‐rich peptides assessed by optical spectroscopies: Effect of chain length, concentration, solvent, and time

Solution secondary structures of three synthetic cationic peptides, currently used in antisense oligonucleotide delivery into living cells, have been analyzed by means of circular dichroism (CD) and Raman scattering in different buffers as a function of concentration and time. All three peptides are of minimalist conception, i.e., formed by only two types of amino acids (leucine: L and lysine: K). Two of these peptides contain 15 aminoacids: N ter ‐ KLLKLLLKLLLKLLK (L 10 K 5 ), N ter ‐KLKLKLKLKLKLKLK (L 7 K 8 ), and the third one has only 9 residues: N ter ‐KLKLKLKLK (L 4 K 5 ). The conformational behavior of the 15‐mers in pure water differs considerably one from another. Although both of them are initially disordered in the 50–350 μM range, L 10 K 5 gradually undergoes a disordered to α ‐helix transition for molecular concentrations above 100 μM. In all other solvents used, L 10 K 5 adopts a stable α ‐helical conformation. In methanol and methanol/Tris mixture, nonnative α ‐helices can be induced in both KL‐alternating peptides, i.e., L 7 K 8 and L 4 K 5 . However, in major cases and with a time delay depending on peptide concentration, β ‐like structures can be gradually formed in both solutions. In PBS and methanol/PBS mixture, the tendency for L 7 K 8 and L 4 K 5 is to form structures belonging to β ‐family. A discussion has been undertaken on the effect of counterions as well as their nature in the stabilization of ordered structures in both KL‐alternating peptides. © 2005 Wiley Periodicals, Inc. Biopolymers 81: 8–19, 2006 This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com