Cellular Uptake Studies with β-Peptides

✍ Scribed by Magnus Rueping; Yogesh Mahajan; Markus Sauer; Dieter Seebach

• Book ID: 101354904
• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 85 KB
• Volume: 3
• Category: Article
• ISSN: 1439-4227
• DOI: 10.1002/1439-7633(20020301)3:2/3<257::aid-cbic257>3.0.co;2-s

✦ Synopsis

b-Peptides have been shown to fold into stable secondary structures similar to those observed in natural peptides and proteins. [1] The finding that bpeptides are completely stable to proteolytic degradation renders them candidates for use as peptido-mimetics. [2] In fact, b-peptides have been demonstrated to mimic a-peptidic hormones, [3] to inhibit cholesterol uptake, [4] and to possess antimicrobial [5] and antiproliferative properties. [6] The bioavailability of pharmacologically active compounds, for instance, peptides and proteins, depends significantly on their physical properties, as their uptake correlates with solubility in the polar extracellular medium and passive diffusion through the nonpolar lipid bilayer. Recently, methods have been developed for the delivery of proteins, biological active compounds, and DNA into living cells with the help of membranepermeable carrier peptides (oligomers containing basic side chains). [7] In order to determine the structural requirements for cellular uptake of b-peptides, a series of fluorescein-labeled b-peptides 1 ± 6 has been prepared (Scheme 1). The substitution pattern of the b-peptides was selected for the following reasons: the b-