Backbone side chain interactions in peptides. II. Solution study of serine-containing model dipeptides

Area of Science:

• Biochemistry
• Structural Biology
• Chemical Physics

Background:

• Serine's high content in beta-folded protein regions suggests specific interactions.
• Previous X-ray studies indicated a proton-donating role for the Ser NH bond in the solid state.

Purpose of the Study:

• Investigate the solution-state behavior of serine-containing dipeptides.
• Determine the role of N--H. . .O gamma interactions in protein secondary structure.
• Analyze the conformational preferences of serine residues.

Main Methods:

• Spectroscopic investigations (NMR, etc.) on five model dipeptides.
• Analysis of L-Pro-D-Ser, L-Pro-L-Ser, L-Ala-L-Ser, L-Ser-L-Ala, and L-Ser-Gly sequences.
• Comparison of solid-state and solution-state structural data.

Main Results:

• The N--H. . .O gamma interaction observed in solid-state structures is partially retained in solution for X-Ser sequences.
• This interaction favors beta-folding in X-Ser sequences.
• In Ser-X sequences, competition with typical beta-turns reduces beta-folding.
• Rotamer III (chi 1 ≈ 60°) is the predominant conformation for the Ser C alpha--C beta bond.

Conclusions:

• The N--H. . .O gamma interaction is crucial for serine's role in beta-folding.
• The sequence context (X-Ser vs. Ser-X) dictates the impact of this interaction on secondary structure.
• Serine's conformational preferences are influenced by intramolecular hydrogen bonding.