Synthesis and conformational studies of a β-turn mimetic incorporated in Leu-enkephalin
2004 (English)In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 69, no 10, 3500-3508 p.Article in journal (Refereed) Published
A β-turn mimetic in which the four amino acids of a β-turn have been replaced by a 10-membered ring has been designed, synthesized, and subjected to conformational studies. In the mimetic, the intramolecular COi − HNi+3 hydrogen bond that is often found in β-turns has been replaced by an ethylene bridge. In addition, the amide bond between residues i and i + 1 was exchanged for a methylene ether isoster. Such a β-turn mimetic, based on the first four residues of Leu-enkephalin (Tyr-Gly-Gly-Phe-Leu), was prepared in 15 steps. The synthesis relied on a β-azido alcohol prepared in five steps from Cbz-Tyr(tBu)-OH as a key, i-position building block. tert-Butyl bromoacetate, glycine, and a Phe-Leu dipetide were then used as building blocks for positions i + 1, i + 2, and i + 3, respectively. Conformational studies based on 1H NMR data showed that the β-turn mimetic was flexible, but that it resembled a type-II β-turn at low temperature. This low energy conformer closely resembled the structure determined for crystalline Leu-enkephalin.
Place, publisher, year, edition, pages
American Chemical Society (ACS), 2004. Vol. 69, no 10, 3500-3508 p.
IdentifiersURN: urn:nbn:se:umu:diva-2273DOI: 10.1021/jo0356863OAI: oai:DiVA.org:umu-2273DiVA: diva2:140202