Conformational and topological requirements of cell-permeable peptide function
| Autor: | Mauricio Rojas, Caigan Du, SongYi Yao, Yao-Zhong Lin |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Signal peptide
Circular dichroism Cell Membrane Permeability Protein Conformation Molecular Sequence Data Peptide Biology Topology Biochemistry Cell membrane Mice Endocrinology Protein structure medicine Animals Amino Acid Sequence Fluorescent Antibody Technique Indirect Peptide library Peptide sequence chemistry.chemical_classification Circular Dichroism Molecular Mimicry Rational design 3T3 Cells medicine.anatomical_structure chemistry Peptides |
| Zdroj: | The Journal of Peptide Research. 51:235-243 |
| ISSN: | 1397-002X |
| DOI: | 10.1111/j.1399-3011.1998.tb01221.x |
| Popis: | Cell-permeable peptide import recently was developed to deliver synthetic peptides into living cells for studying intracellular protein functions. This import process is mediated by an N-terminal carrier sequence which is the hydrophobic region of a signal peptide. In this study, the conformational consequence of the interaction of cell-permeable peptides with different mimetic membrane environments was investigated by circular dichroism analysis. We showed that cell-permeable peptides adopted alpha-helical structures in sodium dodecyl sulfate (SDS) micelles or aqueous trifluoroethanol (TFE). The potency of these peptides in forming helical structures is higher in an amphiphilic environment (SDS) than in a hydrophobic environment (TFE), suggesting that some hydrophilic molecules associated with the cell membrane may be involved in peptide import. We also studied topological requirements of cell-permeable peptide function. We demonstrated that peptides containing the carrier sequence in their C-termini can also be imported into cells efficiently. This important discovery can avoid repetitious synthesis of the membrane-translocating sequence for peptides with different functional cargoes and is potentially useful for developing a cell-permeable peptide library. Finally, we showed that, when a retro version of the carrier sequence was used, the peptide lost its translocating ability despite retaining a high content of alpha-helical structure in mimetic membrane environments. This suggests that the propensity of peptides to adopt a helical conformation is required but not sufficient for cellular import and that other structural factors such as the side-chain topology of the carrier sequence are also important. Our studies together contribute to the more rational design of useful cell-permeable peptides. |
| Databáze: | OpenAIRE |
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