Cyclic Aromatic Amino Acids with Constrained χ1 and χ2 Dihedral Angles

  • Dirk Tourwé
  • Koen Iterbeke
  • Wieslaw M. Kazmierski
  • Géza Tóth
Part of the Methods in Molecular Medicine™ book series (MIMM, volume 23)


The concept of topographic design of peptide neurotransmitters and hormones was pioneered by Hruby (1,2). When the design involved primarily constraint of the side chains of a peptide that has a well-defined backbone conformation, the term “topographic design on a stable template” was proposed (3). The side chain χ1 of aromatic amino acids, such as Phe, Trp, Tyr, and His, can be constrained in either the gauche (−) or gauche (+) conformation by linking the nitrogen atom to the aromatic ring through a methylene bridge (Fig. 1).
Fig. 1.

Principle of side-chain constraint for Phe, Trp, and His.


Aromatic Amino Acid Mandelic Acid Benzoyl Chloride Zwitterionic Form Benzyl Ester 
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Copyright information

© Humana Press Inc., Totowa, NJ 1999

Authors and Affiliations

  • Dirk Tourwé
    • 1
  • Koen Iterbeke
    • 1
  • Wieslaw M. Kazmierski
    • 2
  • Géza Tóth
    • 3
  1. 1.Organic Chemistry DepartmentVrije Universiteit BrusselBrusselsBelgium
  2. 2.Department of Medicinal ChemistryGlaxo Wellcome Research and DevelopmentResearch Triangle Park
  3. 3.Isotope Laboratory, Biological Research CentreHungarian Academy of SciencesSzegedHungary

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