We performed the solution-phase synthesis of a set of model peptides, including homo-oligomers, based on the 2-aminoadamantane-2-carboxylic acid (Adm) residue, an extremely bulky, highly lipophilic, tricyclic, achiral, C-tetrasubstituted -amino acid. In particular, for the difficult peptide coupling reaction between two Adm residues, we took advantage of the Meldal's -azidoacyl chloride approach. Most of the synthesized Adm peptides were characterized by single-crystal X-ray diffraction analyses. The results indicate a significant propensity for the Adm residue to adopt -turn and -turn-like conformations. Interestingly, we found that a -CO-(Adm)(2)-NH- sequence is folded in the crystal state into a regular, incipient -helix, at variance with the behavior of all of the homo-dipeptides from C-tetrasubstituted -amino acids already investigated, which tend to adopt either the -turn or the fully extended conformation. Our density functional theory conformational energy calculations on the terminally blocked homo-peptides (n=2-8) fully confirmed the crystal-state data, strongly supporting the view that this rigid C-tetrasubstituted -amino acid residue is largely the most effective building block for -helix induction, although to a limited length (anti-cooperative effect).

En route towards the peptide g-helix: X-ray diffraction analyses and conformational energy calculations of Adm-rich short peptides

Mazzier, Daniela;Grassi, Luigi;Moretto, Alessandro;Formaggio, Fernando;Toniolo, Claudio
;
Crisma, Marco
2017

Abstract

We performed the solution-phase synthesis of a set of model peptides, including homo-oligomers, based on the 2-aminoadamantane-2-carboxylic acid (Adm) residue, an extremely bulky, highly lipophilic, tricyclic, achiral, C-tetrasubstituted -amino acid. In particular, for the difficult peptide coupling reaction between two Adm residues, we took advantage of the Meldal's -azidoacyl chloride approach. Most of the synthesized Adm peptides were characterized by single-crystal X-ray diffraction analyses. The results indicate a significant propensity for the Adm residue to adopt -turn and -turn-like conformations. Interestingly, we found that a -CO-(Adm)(2)-NH- sequence is folded in the crystal state into a regular, incipient -helix, at variance with the behavior of all of the homo-dipeptides from C-tetrasubstituted -amino acids already investigated, which tend to adopt either the -turn or the fully extended conformation. Our density functional theory conformational energy calculations on the terminally blocked homo-peptides (n=2-8) fully confirmed the crystal-state data, strongly supporting the view that this rigid C-tetrasubstituted -amino acid residue is largely the most effective building block for -helix induction, although to a limited length (anti-cooperative effect).
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11577/3251865
Citazioni
  • ???jsp.display-item.citation.pmc??? 1
  • Scopus 7
  • ???jsp.display-item.citation.isi??? 7
social impact