- Exploring hydrophobicity limits of polyproline helix with oligomeric octahydroindole-2-carboxylic acid
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The polyproline-II helix is the most extended naturally occurring helical structure and is widely present in polar, exposed stretches and “unstructured” denatured regions of polypeptides. Can it be hydrophobic? In this study, we address this question usin
- Kubyshkin, Vladimir,Budisa, Nediljko
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- Construction of a polyproline structure with hydrophobic exterior using octahydroindole-2-carboxylic acid
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The proline analogue (2S,3aS,7aS)-octahydroindole-2-carboxylic acid (Oic) has been previously applied as a proline substitute in pharmocologically active peptides and as a structural component of the antihypertensive drug Perindopril. Herein, we describe the formation of an oligoproline structure by an Oic oligomer. A series of Oic oligomers were investigated to show the structural and energetic contribution of appended residues to the structure. NMR investigation of these oligomers revealed an all-trans amide bond structure, and we provide evidence that a cascade-like mechanism is responsible for the all-trans folding cooperativity. X-ray crystallography of the Oic-hexapeptide clearly demonstrates that the all-trans structure of the Oic oligomer is a polyproline II helix. Thus, as a hydrophobic proline analog with a highly stable trans-amide bond, Oic represents an ideal building block for hydrophobic sites of polyproline II structures in biologically relevant contexts.
- Kubyshkin, Vladimir,Budisa, Nediljko
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p. 619 - 627
(2017/01/25)
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