Conformationally Constrained Histidines in the Design of Peptidomimetics: Strategies for the χ-Space Control
| Autor: | Ivana Cacciatore, Azzurra Stefanucci, F. Pinnen, Adriano Mollica, Gino Lucente, Federica Feliciani |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Cyclopropanes
Models Molecular conformation Stereochemistry Peptidomimetic Review Catalysis Cyclopropane Inorganic Chemistry lcsh:Chemistry chemistry.chemical_compound Structure-Activity Relationship Side chain Structure–activity relationship χ-space Physical and Theoretical Chemistry alkyl substitution Molecular Biology stereoselective synthesis lcsh:QH301-705.5 Spectroscopy Histidine Alkyl chemistry.chemical_classification amino acids Organic Chemistry General Medicine histidine Computer Science Applications Amino acid Protein Structure Tertiary chemistry lcsh:Biology (General) lcsh:QD1-999 Peptidomimetics Pharmacophore |
| Zdroj: | International Journal of Molecular Sciences, Vol 12, Iss 5, Pp 2853-2890 (2011) International Journal of Molecular Sciences |
| ISSN: | 1422-0067 |
| Popis: | 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 χ(1) and χ(2) 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 C(α)-C(β) cyclopropane insertion (ACC derivatives). Attention is also dedicated to the relevant field of β-aminoacid chemistry by describing the synthesis of β(2)- and β(3)-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. |
| Databáze: | OpenAIRE |
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