A fluoro-alkene mimic of Gly-<i>trans</i>-Pro produces a stable collagen triple helix

Alkene dipeptide isosteres (ADIs) are promising surrogates of peptide bonds that enhance the bioactive peptide resistance to enzymatic hydrolysis in medicinal chemistry. In this study, we investigated the substitution effects of an ADI on the energy barrier of cis-trans isomerization in the acetyl proline methyl ester (Ac-Pro-OMe) model. The (E)-alkene-type proline analog, which favors a cis-amide conformation, exhibits a lower rotational barrier than native Ac-Pro-OMe. A van't Hoff analysis suggests that the energy barrier is primarily reduced by enthalpic repulsion. It was concluded that although carbon-carbon double bonds and pyrrolidine rings individually increase the rigidity of the incorporation site, their combination can provide structural flexibility and disrupt bioactive conformations. This work provides new insights into ADI-based drug design.

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A fluoro-alkene mimic of Gly-trans-Pro produces a stable collagen triple helix

Abstract: We report the first experimental evidence for a fluoro-alkene amide isostere participating in n→π* donation, which stabilizes the collagen triple helix. Of the three amide positions in canonical collagen-like peptides,...

Cited by 2 publications

References 40 publications

Gold-catalyzed hydrofluorination of terminal alkynes using potassium bifluoride (KHF₂)

Gold-catalyzed hydrofluorination of terminal alkynes using potassium bifluoride (KHF₂)

Substitution Effects of Alkene Dipeptide Isosteres on Adjacent Peptide Bond Rotation

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A fluoro-alkene mimic of Gly-trans-Pro produces a stable collagen triple helix

Abstract: We report the first experimental evidence for a fluoro-alkene amide isostere participating in n→π* donation, which stabilizes the collagen triple helix. Of the three amide positions in canonical collagen-like peptides,...

Cited by 2 publications

References 40 publications

Gold-catalyzed hydrofluorination of terminal alkynes using potassium bifluoride (KHF2)

Gold-catalyzed hydrofluorination of terminal alkynes using potassium bifluoride (KHF2)

Substitution Effects of Alkene Dipeptide Isosteres on Adjacent Peptide Bond Rotation

Contact Info

Product

Resources

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Gold-catalyzed hydrofluorination of terminal alkynes using potassium bifluoride (KHF₂)

Gold-catalyzed hydrofluorination of terminal alkynes using potassium bifluoride (KHF₂)