Cyclohexane ring as a tool to select the presentation of the carbohydrate moiety in glycosyl amino acids |
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Authors: | Rodríguez Fernando Somovilla Víctor J Corzana Francisco Busto Jesús H Avenoza Alberto Peregrina Jesús M |
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Institution: | Departamento de Química, Universidad de La Rioja, Centro de Investigación en Síntesis Química, UA-CSI, Madre de Dios, 51, 26006 Logro?o, Spain. |
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Abstract: | The design of mimic molecules that resemble natural products can be a useful tool to help understand the key aspects in molecular recognition processes that are difficult to access by using natural derivatives. We present the synthesis and the conformational analysis of different glucosylated diamide amino acids that simulate glycopeptides with β-O-linked glucose and contain the nonnatural β-hydroxycyclohexane-α-amino acid. The study, using NMR experiments, X-ray spectroscopy, and molecular dynamics simulations, reveals that the cyclohexane ring allows some naturally occurring ways of presentation of the carbohydrate to be fixed, or to stabilize some novel conformations. In addition, different chair conformations for the cyclohexane-α-amino acid moiety can be set, in particular, those with high population of conformers in which the bulky groups are located at axial positions. Moreover, to increase the scope of these cyclohexane derivatives, two dipeptides incorporating the glycomimics have been synthesized and further glycosylated to obtain the corresponding α-O-glycopeptides. These features can have important implications for the design of new drugs and for understanding the complex molecular processes that take place between glycopeptides and their biological targets. |
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