Comparison of Penetratin and Other Homeodomain-Derived Cell-Penetrating Peptides: Interaction in a Membrane-Mimicking Environment and Cellular Uptake Efficiency

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• 作者：Sté ; phane Balayssac ; Fabienne Burlina ; Odile Convert ; Gé ; rard Bolbach ; Gé ; rard Chassaing ; and Olivier Lequin
• 刊名：Biochemistry
• 出版年：2006
• 出版时间：February 7, 2006
• 年：2006
• 卷：45
• 期：5
• 页码：1408 - 1420
• 全文大小：654K
• 年卷期：v.45,no.5(February 7, 2006)
• ISSN：1520-4995

文摘

Antennapedia and other homeoproteins have the unique ability to efficiently translocate acrossbiological membranes, a property that is mediated by the third helix of the homeodomain. To analyze theeffects of sequence divergence in the homeodomain, we have compared the cellular uptake efficienciesand interaction properties in a membrane-mimicking environment of four peptides corresponding to thethird helix sequence of Antennapedia, Engrailed-2, HoxA-13, and Knotted-1. NMR studies revealed thatthese peptides adopt helical conformations in SDS micelles. Their localization with respect to the micellewas investigated using Mn²⁺ as a paramagnetic probe. Peptides are positioned parallel to the micellesurface, but subtle differences in the depth of immersion were observed. Using a recently developedmethod for quantification of CPP cellular uptake based on MALDI-TOF mass spectrometry, all of thesepeptides were found to translocate into cells but with large differences in their uptake efficiencies. Thepeptide with the highest uptake efficiency was found to be the least deeply inserted within the micelle,indicating that electrostatic surface interactions may be a major determinant for membrane translocation.A new cell-penetrating peptide derived from Knotted-1 homeodomain with improved uptake propertiescompared to penetratin is introduced here.