The conformational preferences of γ-lactam and its role in constraining peptide structure

✍ Scribed by P. K. C. Paul; P. A. Burney; M. M. Campbell; D. J. Osguthorpe

• Publisher: Springer Netherlands
• Year: 1990
• Tongue: English
• Weight: 849 KB
• Volume: 4
• Category: Article
• ISSN: 0920-654X
• DOI: 10.1007/bf00125013

✦ Synopsis

The conformational constraints imposed by 7-1actams in peptides have been studied using valence force field energy calculations and flexible geometry maps. It has been found that while cyclisation restrains the ~u of the lactam, non-bonded interactions contribute to the constraints on ~0 of the lactam. The ~-lactam also affects the (~0,~,) of the residue after it in a peptide sequence. For an L-lactam, the ring geometry restricts q/ to about -120 °, and ~0 has two minima, the lowest energy around -140 ° and a higher minimum (5 kcal/mol higher) at 60 °, making an L-~-lactam more favourably accommodated in a near extended conformation than in position 2 of a type II' t-turn. The energy of the (0 ~ + 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-~-lactam. The ((0,V/) maps of the residue succeeding a ?-lactam show subtle differences from those of standard N-methylated residues. The dependence of the constraints on the chirality of ?-lactams and N-substituted 7-1actams, in terms of the formation of secondary structures like t-turns is discussed and the comparison of the theoretical conformations with experimental results is highlighted.