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Progress in Chemistry 2016, Vol. 28 Issue (7): 1084-1098 DOI: 10.7536/PC160107 Previous Articles   Next Articles

• Review and comments •

The Conformational Restriction of β-Peptidomimetics in Drug Design

Yuan Shuo, Sun Dequn*   

  1. Marine College, Shandong University, Weihai, Weihai 264209, China
  • Received: Revised: Online: Published:
  • Supported by:
    The work was supported by the National Natural Science Foundation of China (No.21472243).
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The traditional peptide drugs are unstable in vivo conditions due to hydrolysis. The β-peptide that composed of β-amino acids has improved pharmacokinetic parameters than α-peptide and is valuable in drug development. The conformation restricted β-amino acids can form the β-peptidomimetics in order to improve its biological activity and metabolic stability. The restricted β-peptidomimetics can form fixed secondary structure and fold with specific way, then it has an ideal three-dimensional structure and embed in specific enzymes or receptors eventually. This review describes the methods of conformational restriction and the changes of biological activity or physical and chemical parameters after conformational restriction for β-peptidomimetics. Two kinds of conformationally restricted β-peptidomimetics including the local conformational restriction and the overall cyclization of β-peptidomimetics are reviewed. This paper could provide guidance for the rational design of β-peptide drugs.

Contents
1 Introduction
2 Local conformational restriction of β-peptides
2.1 Monoalkylating β2 or β3-amino acids
2.2 Dialkylating β2,3-amino acids
2.3 Cα-fluorinated β-amino acids
2.4 N-substituted β-amino acids
2.5 Ring substituted β-amino acids
3 The overall cyclization of β-peptides
3.1 Cyclization between the head and tail
3.2 Cyclization between the side chains
4 Research methods of the conformational restriction
4.1 Circular dichroism spectroscopy
4.2 Infrared spectroscopy
4.3 X-ray diffraction analysis
4.4 Nuclear magnetic resonance
4.5 Theoretical calculations
5 Conclusion

Key words: β-peptidomimetics, conformational restriction, biological activity, peptide drug design

CLC Number: 

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