| Autor: |
Paul, P. K. C., Burney, P. A., Campbell, M. M., Osguthorpe, D. J. |
| Zdroj: |
Journal of Computer-Aided Molecular Design; September 1990, Vol. 4 Issue: 3 p239-253, 15p |
| Abstrakt: |
Summary The conformational constraints imposed by γ-lactams in peptides have been studied using valence force field energy calculations and flexible geometry maps. It has been found that while cyclisation restrains the Ψ of the lactam, non-bonded interactions contribute to the constraints on ϕ of the lactam. The γ-lactam also affects the (ϕ,Ψ) of the residue after it in a peptide sequence. For an l-lactam, the ring geometry restricts Ψ to about-120°, and ϕ has two minima, the lowest energy around-140° and a higher minimum (5 kcal/mol higher) at 60°, making an l-γ-lactam more favourably accommodated in a near extended conformation than in position 2 of a type II′ β-turn. The energy of the ϕ∼+60° minimum can be lowered substantially until it is more favoured than the-140° minimum by progressive substitution of bulkier groups on the amide N of the l-γ-lactam. The (ϕ,Ψ) maps of the residue succeeding a γ-lactam show subtle differences from those of standard N-methylated residues. The dependence of the constraints on the chirality of γ-lactams and N-substituted γ-lactams, in terms of the formation of secondary structures like β-turns is discussed and the comparison of the theoretical conformations with experimental results is highlighted. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
Full text from SpringerLink