Evaluation of stereochemically dense morpholine-based scaffolds as proline surrogates in beta-turn peptides.
Four peptides differing for the structure of the new morpholine-based heterocyclic compound acting as a turn inducer were synthesized in solution phase, and the conformational preferences were assessed by means of NMR analysis. All spectroscopic data revealed an adaptive behaviour of the turn peptides in generating turn conformations stabilized by intramolecular hydrogen-bonds, despite the conformational changes of the turn inducer. Thus, this study suggests the possibility of functionalizing morpholine-containing beta-turn peptides with no significant loss of the secondary framework. The 3,4-dihydro-2H-[1,4]oxazine-containing peptide showed a more compact structure stabilized by an additional gamma-turn-forming hydrogen-bond experienced by the Gly amide proton.
Department of Organic Chemistry Ugo Schiff, University of Florence, Via della Lastruccia 13, I-50019, Sesto Fiorentino (FI), Italy.
Filippo
F
Sladojevich
Antonio
A
Guarna
Andrea
A
Trabocchi
D018360:Crystallography, X-Ray; D009025:Morpholines / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry; D011392:Proline / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D009025:Morpholines; D010455:Peptides; C037574:morpholine; D011392:Proline