Cyclohexane ring as a tool to select the presentation of the carbohydrate moiety in glycosyl amino acids

  1. Rodríguez, F. 1
  2. Somovilla, V.J. 1
  3. Corzana, F. 1
  4. Busto, J.H. 1
  5. Avenoza, A. 1
  6. Peregrina, P.J.M. 1
  1. 1 Universidad de La Rioja
    info

    Universidad de La Rioja

    Logroño, España

    ROR https://ror.org/0553yr311

Revue:
Chemistry - A European Journal

ISSN: 0947-6539

Année de publication: 2012

Volumen: 18

Número: 16

Pages: 5096-5104

Type: Article

DOI: 10.1002/CHEM.201103089 PMID: 22383378 SCOPUS: 2-s2.0-84859589651 WoS: WOS:000302354500039 GOOGLE SCHOLAR

D'autres publications dans: Chemistry - A European Journal

Résumé

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. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.