Proline N-oxides: modulators of the 3D conformation of linear peptides through "NO-turns".
Small peptides are essential mediators of numerous physiological processes. Consequently, there is huge interest in the de novo design of peptides with a predictable folding and related biological activity. In this study, we investigate the possibility of modulating the secondary structure of tetrapeptides through proline N-oxide moieties and N-methylation of the peptide backbone. A series of tetrapeptides were synthesised to investigate the combined effect of Pro N-oxide and N-methylation of the amide bond on the (n + 1) residue in terms of cis- and trans-isomerization, as well as how these modifications direct potential intramolecular hydrogen bonding interactions. The right combination of both these parameters led to a trans to cis-conformational interconversion and a change in the nature of the hydrogen bonding interactions, as demonstrated by NMR spectroscopic, molecular modeling analysis and thermal coefficient studies. Proline N-oxide residues were proposed to induce turns we named as NO-γ-turns and NO-β-turns based on their similarity to traditional γ- and β-turns.
Catalysis and Peptide Research Unit, School of Health Sciences, University of Kwazulu-Natal, Durban 4001, South Africa.
Majid D
MD
Farahani
Bahareh
B
Honarparvar
Fernando
F
Albericio
Glenn E M
GE
Maguire
Thavendran
T
Govender
Per I
PI
Arvidsson
Hendrik G
HG
Kruger
D000595:Amino Acid Sequence; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010087:Oxides / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011392:Proline / Q000737:chemistry*; D017433:Protein Structure, Secondary; D066244:Proton Magnetic Resonance Spectroscopy; D011522:Protons; D013816:Thermodynamics
D010087:Oxides; D010455:Peptides; D011522:Protons; D011392:Proline