Abstract
The use of substituted cyclopropanes as conformationally constrained peptidomimetics has received considerable attention recently (1–6). 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 (7–10). 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.
Leu-Enkephalin analog 1.
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Martin, S. F. and Dwyer, M. P., unpublished results.
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Dwyer, M.P., Martin, S.F. (1999). Synthesis of Cyclopropane-Containing Leu-Enkephalin Analogs. In: Kazmierski, W.M. (eds) Peptidomimetics Protocols. Methods in Molecular Medicine™, vol 23. Humana Press. https://doi.org/10.1385/0-89603-517-4:407
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DOI: https://doi.org/10.1385/0-89603-517-4:407
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