Part of the Methods in Molecular Medicine™ book series (MIMM, volume 23)
Synthesis of Cyclopropane-Containing Leu-Enkephalin Analogs
The use of substituted cyclopropanes as conformationally constrained peptidomimetics has received considerable attention recently (1, 2, 3, 4, 5, 6). The efforts from our laboratory in this area have focused on the use 1,2,3-trisubstituted cyclopropanes as novel isosteric replacements in several biological systems (7, 8, 9, 10). A common theme of this program has been the use of trans-substituted cyclopropanes to enforce extended or “β-strand” secondary structure while orienting the amino acid side chain in a predictable conformation (11). In an effort to explore further the utility of this novel isostere, modeling and calculations suggested that a cis-substituted cyclopropane dipeptide subunit could stabilize a turn structure. The focus of this chapter is to describe the preparation of a novel cyclopropane-containing cis-substituted (-Glyψ[CHOH-cp-CONH]-) subunit, which replaces Gly2-Gly3 subunit of the Leu-enkephalin (Tyr-Gly-Gly-Phe-Leu) framework shown in Fig. 1.
KeywordsOrganic Layer Magnesium Sulfate Flash Chromatography Ethylcarbodiimide Hydrochloride Saturated Aqueous NaHCO3
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