Major Factors for the Persistent Folding of Hybrid α, β, γ-Hybrid Peptides Into Hairpins
Factors responsible for the persistent adoption of hairpin conformations by hybrid oligopeptides, each having a central β/α dipeptide segment flanked by aromatic γ-amino acid (γAr) residues, are probed. Our recent studies revealed that tetrapeptide 1 and 2, having central dipeptide segments consisti...
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| Format: | Article |
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Frontiers Media S.A.
2020-09-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fchem.2020.530083/full |
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| author | Yulong Zhong Quan Tang Daniel P. Miller Eva Zurek Rui Liu Zhong-Lin Lu Bing Gong |
| author_facet | Yulong Zhong Quan Tang Daniel P. Miller Eva Zurek Rui Liu Zhong-Lin Lu Bing Gong |
| author_sort | Yulong Zhong |
| collection | DOAJ |
| description | Factors responsible for the persistent adoption of hairpin conformations by hybrid oligopeptides, each having a central β/α dipeptide segment flanked by aromatic γ-amino acid (γAr) residues, are probed. Our recent studies revealed that tetrapeptide 1 and 2, having central dipeptide segments consisting of β-alanine (β-Ala) and glycine (Gly), and L-β-homophenylalanine (L-β-homoPhe) and Gly residues, respectively, that are flanked by γAr residues, fold into well-defined, expanded β-turns with doubly H-bonded γAr residues. Replacing the γAr residues of 1 and 2 with L-Val and L-Leu residues results in tetrapetides 1′ and 2′ that fail to fold into defined conformations, which confirms the decisive role played by the H-bonded γAr residues in the promoting folding of 1 and 2. Attaching L-Val and L-Leu residues to the termini of 1 affords hexapeptide 1a. With an additional H-bond between its L-Val and L-Leu residues, peptide 1a folds into a hairpin with higher stability than that of 1, indicating that the expanded β-turn can nucleate and stabilize β-hairpin with longer β-strands. Attaching L-Val and L-Leu residues to the termini of 2 affords hexapeptide 2a. Substituting the L-β-homoPhe residue of 2a with a D-β-homoPhe residue gives hexapeptide 2b. Surprisingly, hexapeptide 2a fold into a hairpin showing the similar stability as those of tetrapeptides 1 and 2. Hexapeptide 2b, with its combination of a D-β-homoPhe residue and the L-Val/L-Leu pair, fold into a hairpin that is significantly more stable than the other hybrid peptides, demonstrating that a combination of hetero-chirality between the β-amino acid residue of the dipeptide loop and the α-amino acid residues of the β-strands enhances the stability of the resultant β-hairpin. |
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| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-12-10T10:32:29Z |
| publishDate | 2020-09-01 |
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| spelling | doaj.art-7d24385499304b4cbd87f11496b0dd8d2022-12-22T01:52:31ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462020-09-01810.3389/fchem.2020.530083530083Major Factors for the Persistent Folding of Hybrid α, β, γ-Hybrid Peptides Into HairpinsYulong Zhong0Quan Tang1Daniel P. Miller2Eva Zurek3Rui Liu4Zhong-Lin Lu5Bing Gong6Department of Chemistry, University at Buffalo, The State University of New York, Buffalo, NY, United StatesCollege of Chemistry, Beijing Normal University, Beijing, ChinaDepartment of Chemistry, Hofstra University, Hempstead, NY, United StatesDepartment of Chemistry, University at Buffalo, The State University of New York, Buffalo, NY, United StatesCollege of Chemistry, Beijing Normal University, Beijing, ChinaCollege of Chemistry, Beijing Normal University, Beijing, ChinaDepartment of Chemistry, University at Buffalo, The State University of New York, Buffalo, NY, United StatesFactors responsible for the persistent adoption of hairpin conformations by hybrid oligopeptides, each having a central β/α dipeptide segment flanked by aromatic γ-amino acid (γAr) residues, are probed. Our recent studies revealed that tetrapeptide 1 and 2, having central dipeptide segments consisting of β-alanine (β-Ala) and glycine (Gly), and L-β-homophenylalanine (L-β-homoPhe) and Gly residues, respectively, that are flanked by γAr residues, fold into well-defined, expanded β-turns with doubly H-bonded γAr residues. Replacing the γAr residues of 1 and 2 with L-Val and L-Leu residues results in tetrapetides 1′ and 2′ that fail to fold into defined conformations, which confirms the decisive role played by the H-bonded γAr residues in the promoting folding of 1 and 2. Attaching L-Val and L-Leu residues to the termini of 1 affords hexapeptide 1a. With an additional H-bond between its L-Val and L-Leu residues, peptide 1a folds into a hairpin with higher stability than that of 1, indicating that the expanded β-turn can nucleate and stabilize β-hairpin with longer β-strands. Attaching L-Val and L-Leu residues to the termini of 2 affords hexapeptide 2a. Substituting the L-β-homoPhe residue of 2a with a D-β-homoPhe residue gives hexapeptide 2b. Surprisingly, hexapeptide 2a fold into a hairpin showing the similar stability as those of tetrapeptides 1 and 2. Hexapeptide 2b, with its combination of a D-β-homoPhe residue and the L-Val/L-Leu pair, fold into a hairpin that is significantly more stable than the other hybrid peptides, demonstrating that a combination of hetero-chirality between the β-amino acid residue of the dipeptide loop and the α-amino acid residues of the β-strands enhances the stability of the resultant β-hairpin.https://www.frontiersin.org/article/10.3389/fchem.2020.530083/fullhybrid peptidefoldamerhydrogen bondβ-turnunnatural amino acidβ-hairpin |
| spellingShingle | Yulong Zhong Quan Tang Daniel P. Miller Eva Zurek Rui Liu Zhong-Lin Lu Bing Gong Major Factors for the Persistent Folding of Hybrid α, β, γ-Hybrid Peptides Into Hairpins Frontiers in Chemistry hybrid peptide foldamer hydrogen bond β-turn unnatural amino acid β-hairpin |
| title | Major Factors for the Persistent Folding of Hybrid α, β, γ-Hybrid Peptides Into Hairpins |
| title_full | Major Factors for the Persistent Folding of Hybrid α, β, γ-Hybrid Peptides Into Hairpins |
| title_fullStr | Major Factors for the Persistent Folding of Hybrid α, β, γ-Hybrid Peptides Into Hairpins |
| title_full_unstemmed | Major Factors for the Persistent Folding of Hybrid α, β, γ-Hybrid Peptides Into Hairpins |
| title_short | Major Factors for the Persistent Folding of Hybrid α, β, γ-Hybrid Peptides Into Hairpins |
| title_sort | major factors for the persistent folding of hybrid α β γ hybrid peptides into hairpins |
| topic | hybrid peptide foldamer hydrogen bond β-turn unnatural amino acid β-hairpin |
| url | https://www.frontiersin.org/article/10.3389/fchem.2020.530083/full |
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