Further Evidence for 2-Alkyl-2-carboxyazetidines as γ-Turn Inducers
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- 作者：Jos Luis Baeza ; Guillermo Gerona-Navarro ; Kevin Thompson ; M. Jess Prez de Vega ; Lourdes Infantes ; M. Teresa Garca-Lpez ; Rosario Gonzlez-Muiz ; Mercedes Martn-Martnez
- 刊名：Journal of Organic Chemistry
- 出版年：2009
- 出版时间：November 6, 2009
- 年：2009
- 卷：74
- 期：21
- 页码：8203-8211
- 全文大小：917K
- 年卷期：v.74,no.21(November 6, 2009)
- ISSN：1520-6904
文摘
Reverse turns, a common motif in proteins and peptides, have attracted attention due to their relevance in a wide variety of biological processes. In an attempt to artificially imitate and stabilize these turns in short peptides, we have developed versatile synthetic methodologies for the preparation of 2-alkyl-2-carboxyazetidines and incorporated them into the i + 1 position of model tetrapeptides, where they have shown a tendency to induce γ-turns. However, to ascertain the general utility of these restricted amino acids as γ-type reverse turn inducers, it was then required to study the conformational preferences when located at other positions. To this end, model tetrapeptides R-CO-Ala-Xaa-NHMe, containing differently substituted azetidine moieties (Xaa = Aze, 2-MeAze, 2-BnAze) at the i + 2 position, were synthesized and subjected to a thorough conformational analysis. The theoretical and experimental results obtained, including the X-ray diffraction structure of a dipeptide derivative containing this skeleton, provide evidence that the 2-alkyl-2-carboxyazetidine scaffold is able to efficiently induce γ-turns when incorporated into these short peptides, irrespective of their localization in the peptide chain.