IBTM-Containing Gramicidin S Analogues: Evidence for IBTM as a Suitable Type II' -Turn Mimetic
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- 作者：David Andreu ; Sergi Ruiz ; Cristina Carreñ ; o ; Jordi Alsina ; Fernando Albericio ; Marí ; a Á ; ngeles Jimé ; nez ; Natalia de la Figuera ; Rosario Herranz ; Marí ; a Teresa Garcí
- 刊名：Journal of the American Chemical Society
- 出版年：1997
- 出版时间：November 5, 1997
- 年：1997
- 卷：119
- 期：44
- 页码：10579 - 10586
- 全文大小：319K
- 年卷期：v.119,no.44(November 5, 1997)
- ISSN：1520-5126
文摘
The2-amino-3-oxohexahydroindolizino[8,7-b]indole-5-carboxylatesystem (IBTM) has been proposed asa dipeptide surrogate of type II' 
-turns. To evaluate which ofthe 11bR and 11bS diastereomers of IBTMbestreproduces the conformational properties of type II' -turns,gramicidin S (GS), a cyclic antibiotic peptide thatcontainstwo such units, has been chosen as a test compound and the effect ofeither diastereomer on both conformation andactivity of the resulting peptide analogues has been determined. Aconventional approach to the cyclic peptidestructure based on solution cyclization of a partially protectedprecursor was only practicable for the (S)-IBTMdiastereomer. As an alternative, a solid phase mediatedcyclization approach has been devised and appliedsuccessfullyto both gramicidin S and its Lys2,2' analogue, thenextended to the (R)-IBTM-containing analogues.NMRconformational analysis has clearly shown that only the (R)diastereomer of IBTM is a suitable mimic of the typeII' -turn conformation typical of GS. Differences inantibacterial activity between the (S)- and(R)-IBTM-containingGS analogues confirm the conformational results.
-turns. To evaluate which ofthe 11bR and 11bS diastereomers of IBTMbestreproduces the conformational properties of type II' -turns,gramicidin S (GS), a cyclic antibiotic peptide thatcontainstwo such units, has been chosen as a test compound and the effect ofeither diastereomer on both conformation andactivity of the resulting peptide analogues has been determined. Aconventional approach to the cyclic peptidestructure based on solution cyclization of a partially protectedprecursor was only practicable for the (S)-IBTMdiastereomer. As an alternative, a solid phase mediatedcyclization approach has been devised and appliedsuccessfullyto both gramicidin S and its Lys2,2' analogue, thenextended to the (R)-IBTM-containing analogues.NMRconformational analysis has clearly shown that only the (R)diastereomer of IBTM is a suitable mimic of the typeII' -turn conformation typical of GS. Differences inantibacterial activity between the (S)- and(R)-IBTM-containingGS analogues confirm the conformational results.