Next Article in Journal
Previous Article in Journal
Int. J. Mol. Sci. 2011, 12(5), 2853-2890; doi:10.3390/ijms12052853
Review

Conformationally Constrained Histidines in the Design of Peptidomimetics: Strategies for the χ-Space Control

1, 1, 1, 1, 2 and 1,*
Received: 31 March 2011; in revised form: 18 April 2011 / Accepted: 20 April 2011 / Published: 3 May 2011
(This article belongs to the Special Issue Peptidomimetics)
View Full-Text   |   Download PDF [545 KB, updated 19 June 2014; original version uploaded 19 June 2014]
Abstract: A successful design of peptidomimetics must come to terms with χ-space control. The incorporation of χ-space constrained amino acids into bioactive peptides renders the χ1 and χ2 torsional angles of pharmacophore amino acids critical for activity and selectivity as with other relevant structural features of the template. This review describes histidine analogues characterized by replacement of native α and/or β-hydrogen atoms with alkyl substituents as well as analogues with α, β-didehydro unsaturation or Cα-Cβ cyclopropane insertion (ACC derivatives). Attention is also dedicated to the relevant field of β-aminoacid chemistry by describing the synthesis of β2- and β3-models (β-hHis). Structural modifications leading to cyclic imino derivatives such as spinacine, aza-histidine and analogues with shortening or elongation of the native side chain (nor-histidine and homo-histidine, respectively) are also described. Examples of the use of the described analogues to replace native histidine in bioactive peptides are also given.
Keywords: amino acids; alkyl substitution; conformation; histidine; stereoselective synthesis; χ-space amino acids; alkyl substitution; conformation; histidine; stereoselective synthesis; χ-space
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Export to BibTeX |
EndNote


MDPI and ACS Style

Stefanucci, A.; Pinnen, F.; Feliciani, F.; Cacciatore, I.; Lucente, G.; Mollica, A. Conformationally Constrained Histidines in the Design of Peptidomimetics: Strategies for the χ-Space Control. Int. J. Mol. Sci. 2011, 12, 2853-2890.

AMA Style

Stefanucci A, Pinnen F, Feliciani F, Cacciatore I, Lucente G, Mollica A. Conformationally Constrained Histidines in the Design of Peptidomimetics: Strategies for the χ-Space Control. International Journal of Molecular Sciences. 2011; 12(5):2853-2890.

Chicago/Turabian Style

Stefanucci, Azzurra; Pinnen, Francesco; Feliciani, Federica; Cacciatore, Ivana; Lucente, Gino; Mollica, Adriano. 2011. "Conformationally Constrained Histidines in the Design of Peptidomimetics: Strategies for the χ-Space Control." Int. J. Mol. Sci. 12, no. 5: 2853-2890.



Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert