Impact of Dehydroamino Acids on the Structure and Stability of Incipient 3₁₀-Helical Peptides.

ABSTRACT: A comparative study of the impact of small, medium-sized, and bulky ?,?-dehydroamino acids (?AAs) on the structure and stability of Balaram's incipient 3₁₀-helical peptide (1) is reported. Replacement of the N-terminal Aib residue of 1 with a ?AA afforded peptides 2a-c that maintained the 3₁₀-helical shape of 1. In contrast, installation of a ?AA in place of Aib-3 yielded peptides 3a-c that preferred a ?-sheet-like conformation. The impact of the ?AA on peptide structure was independent of size, with small (?Ala), medium-sized (Z-?Abu), and bulky (?Val) ?AAs exerting similar effects. The proteolytic stabilities of 1 and its analogs were determined by incubation with Pronase. Z-?Abu and ?Val increased the resistance of peptides to proteolysis when incorporated at the 3-position and had negligible impact on stability when placed at the 1-position, whereas ?Ala-containing peptides degraded rapidly regardless of position. Exposure of peptides 2a-c and 3a-c to the reactive thiol cysteamine revealed that ?Ala-containing peptides underwent conjugate addition at room temperature, while Z-?Abu- and ?Val-containing peptides were inert even at elevated temperatures. These results suggest that both bulky and more accessible medium-sized ?AAs should be valuable tools for bestowing rigidity and proteolytic stability on bioactive peptides.

SUBMITTER: Joaquin D 

PROVIDER: S-EPMC7077758 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature