Azetidine-Derived Amino Acids versus Proline Derivatives. Alternative Trends in Reverse Turn Induction

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• 作者：José ; Luis Baeza ; Guillermo Gerona-Navarro ; M. Jesú ; s Pé ; rez de Vega ; M. Teresa Garcí ; a-L&oacute ; pez ; Rosario Gonzá ; lez-Mu&ntilde ; iz ; Mercedes Martí ; n-Martí ; ne
• 刊名：Journal of Organic Chemistry
• 出版年：2008
• 出版时间：March 7, 2008
• 年：2008
• 卷：73
• 期：5
• 页码：1704 - 1715
• 全文大小：377K
• 年卷期：v.73,no.5(March 7, 2008)
• ISSN：1520-6904

文摘

LE>GR ID=jo701746wn00001>ls/joceah/73/i05/figures/jo701746wn00001.gif" ALIGN="left" HSPACE=5>The influence of 2-alkyl-2-carboxyazetidines (Aze) on the 3D structure of model tetrapeptides R²CO-2-R¹Aze-L-Ala-NHMe has been analyzed by molecular modeling, ¹H NMR, and FT-IR studies. Theconformational constraints introduced by the four-membered ring resulted in an effective way to stabilizeges/gifchars/gamma.gif" BORDER=0 >-turn-like conformations in these short peptides. The conformational preferences of these Aze-containingpeptides have been compared to those of the corresponding peptide analogues containing Pro or ges/gifchars/alpha.gif" BORDER=0>-MeProin the place of 2-alkyl-Aze residue. In the model studied, both Pro and Aze derivatives are able to inducereverse turns, but the nature of the turn is different as a function of the ring size. While the five-memberedring of Pro tends to induce ges/gifchars/beta2.gif" BORDER=0 ALIGN="middle">-turns, as previously suggested by different authors, the four-membered ringof Aze residues forces the peptide to preferentially adopt ges/gifchars/gamma.gif" BORDER=0 >-turn conformations. In both cases, the presenceof an alkyl group at the ges/gifchars/alpha.gif" BORDER=0>-position of Pro or the azetidine-2-carboxylate ring enhances significantly theturn-inducing ability. These results might open the opportunity of using 2-alkyl-Aze residues as versatiletools in defining the role of ges/gifchars/gamma.gif" BORDER=0 >-turn structures within the bioactive conformation of selected peptides, andrepresent an alternative to Pro derivatives as turn inducers.