Twists or turns: stabilising alpha
| Autor: | Huy N, Hoang, Timothy A, Hill, Gloria, Ruiz-Gómez, Frederik, Diness, Jody M, Mason, Chongyang, Wu, Giovanni, Abbenante, Nicholas E, Shepherd, David P, Fairlie |
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| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | Chemical Science |
| ISSN: | 2041-6520 |
| Popis: | Twisting or turning peptides: ring size and chi angle in side chain cross-linked tetrapeptides together control α- or β-turn structures, which mimic irregular secondary structures in proteins. Protein–protein interactions involve hotspots as small as 4 sequential amino acids. Corresponding tetrapeptides have no structure in water. Here we report linking side chains of amino acids X and Z to form 24 cyclic tetrapeptides, cyclo-[XAAZ]-NH2, and stabilise 14–18 membered rings that mimic different kinds of non-regular secondary structures found in protein hotspots. 2D NMR spectra allowed determination of 3D structures for 14 cyclic tetrapeptides in water. Five formed two (i, i + 3) hydrogen bonds and a beta/gamma (6, 7) or beta (9, 19, 20) turn; eight formed one (i, i + 4) hydrogen bond and twisted into a non-helical (13, 18, 21, 22, 24) or helical (5, 17, 23) alpha turn; one was less structured (15). A beta or gamma turn was favoured for Z = Dab, Orn or Glu due to a χ1 gauche (+) rotamer, while an alpha turn was favoured for Z = Dap (but not X = Dap) due to a gauche (–) rotamer. Surprisingly, an unstructured peptide ARLARLARL could be twisted into a helix when either a helical or non-helical alpha turn (5, 13, 17, 18, 21–24) with Z = Dap was attached to the N-terminus. These structural models provide insights into stability for different turns and twists corresponding to non-regular folds in protein hotspots. |
| Databáze: | OpenAIRE |
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