Bulky α, β-dehydroamino acids (△AAs) can improve the proteolytic stability of peptides that contain them, presumably by altering the shape of the backbone of the peptide and by stabilizing folded states through their rigidifying effect. The stabilizing effects of △AAs that contain at least one hydrogen atom at the β-carbon are well-known, but the role of bulky ΔAAs that contain fully substituted β-carbons in the stability of larger peptides is less explored. Our lab has developed protocols for the efficient solid-phase peptide synthesis (SPPS) of simple peptides that contain bulky △AAs (△Val and △Env) and now we are working to explore the effects of the bulky △AAs (△Val and △Env) in the stability of larger peptides which are known to form turns or helices. We have synthesized six beta-hairpins and have shown that the bulky △AAs (△Val and △Env) in the <i>i+1</i>/ <i>i+2 </i>postions can induce a beta-turn. We have demonstrated that the bulky △AA containing beta hairpin peptides are significantly stable to proteolysis (2-7 folds) than the controls. This work may pave the way for the efficient and rapid syntheses of stabilized therapeutic agents via SPPS.

Contribution of bulky α, β - dehydroamino acids in the proteolytic stability of beta-hairpins

253rd National Meeting (2017)

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