Sequence and length optimization of membrane active coiled coils for triggered liposome release

Publication date: Available online 10 November 2018Source: Biochimica et Biophysica Acta (BBA) - BiomembranesAuthor(s): Camilla Skyttner, Robert Selegård, Jakob Larsson, Christopher Aronsson, Karin Enander, Daniel AiliAbstractDefined and tunable peptide-lipid membrane interactions that trigger the release of liposome encapsulated drugs may offer a route to improve the efficiency and specificity of liposome-based drug delivery systems, but this require means to tailor the performance of the membrane active peptides. In this paper, the membrane activity of a de novo designed coiled coil peptide has been optimized with respect to sequence and size to improve release efficiency of liposome encapsulated cargo. The peptides were only membrane active when covalently conjugated to the liposomes. Two amino acid substitutions were made to enhance the amphipathic characteristics of the peptide, which increased the release by a factor of five at 1 μM. Moreover, the effect of peptide length was investigated by varying the number of heptad repeats from 2 to 5, yielding the peptides KVC2-KVC5. The shortest peptide (KVC2) showed the least interaction with the membrane and proved less efficient than the longer peptides in releasing the liposomal cargo. The peptide with three heptads (KVC3) caused liposome aggregation whereas KVC4 proved to effectively release the liposomal cargo without causing aggregation. The longest peptide (KVC5) demonstrated the most defined α-helical secondary stru...

Source: Biochimica et Biophysica Acta (BBA) Biomembranes - November 12, 2018 Category: Biochemistry Source Type: research