Stereochemical control of peptide folding

Area of Science:

• Peptide chemistry
• Structural biology
• Biochemistry

Background:

• Stereochemically constrained amino acids can direct peptide backbone conformations.
• Alpha,alpha-dialkyl amino acids are known to stabilize helical structures in synthetic peptides.

Purpose of the Study:

• To review the use of alpha,alpha-dialkyl amino acids in stabilizing helical structures.
• To present strategies for designing well-characterized helical and beta-hairpin peptide structures.

Main Methods:

• Utilizing alpha-aminoisobutyric acid (Aib) and its homologs to promote helix formation.
• Employing 'prime turns' and (D)Pro-Gly segments to nucleate beta-hairpin formation.
• Characterizing peptide structures through crystallographic analysis.

Main Results:

• Alpha,alpha-dialkyl amino acids, such as Aib, facilitate stable helix formation in oligopeptides.
• Crystal structures confirm the helical stabilization provided by these residues.
• Design strategies led to well-characterized beta-hairpin structures, including crystallographic evidence in a synthetic octapeptide.

Conclusions:

• Conformationally rigid helical modules can be designed for applications like helix-linker-helix structures.
• The (D)Pro-Gly approach is effective for generating beta-hairpins and can be extended to larger beta-sheet structures.