Artificial β-sheets: chemical models of β-sheets

Khakshoor, Omid; Nowick, James S.

doi:10.1016/j.cbpa.2008.08.009

Cited by 75 publications

(38 citation statements)

References 56 publications

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“…[1][2][3] Extensive efforts have focused on the design of bioactive macrocyclic peptides containing b-hairpin mimics and binding epitopes for protein-protein and protein-nucleic acid recognitions. [4][5][6] b-Turns are structural motifs defined by four residues at positions i to i 1 3, whose types are classified by the backbone torsion angles / and w of residues i 1 1 and i 1 2. 7 The values of (/ i 1 1 , w i 1 1 , / i 1 2 , w i 1 2 ) are (2608, 2308, 2908, 08) and (2608, 1208, 808, 08) for type I and II b-turns, respectively, whereas the corresponding values are (608, 308, 908, 08) and (608, 21208, 2808, 08) for their mirror-image type I 0 and II 0 bturns, respectively.…”

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confidence: 99%

Propensities of peptides containing the Asn‐Gly segment to form β‐turn and β‐hairpin structures

Kang

Yoo

2016

Biopolymers

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The propensities of peptides that contain the Asn-Gly segment to form β-turn and β-hairpin structures were explored using the density functional methods and the implicit solvation model in CH2 Cl2 and water. The populations of preferred β-turn structures varied depending on the sequence and solvent polarity. In solution, β-hairpin structures with βI' turn motifs were most preferred for the heptapeptides containing the Asn-Gly segment regardless of the sequence of the strands. These preferences in solution are consistent with the corresponding X-ray structures. The sequence, H-bond strengths, solvent polarity, and conformational flexibility appeared to interact to determine the preferred β-hairpin structure of each heptapeptide, although the β-turn segments played a role in promoting the formation of β-hairpin structures and the β-hairpin propensity varied. In the heptapeptides containing the Asn-Gly segment, the β-hairpin formation was enthalpically favored and entropically disfavored at 25°C in water. The calculated results for β-turns and β-hairpins containing the Asn-Gly segment imply that these structural preferences may be useful for the design of bioactive macrocyclic peptides containing β-hairpin mimics and the design of binding epitopes for protein-protein and protein-nucleic acid recognitions. © 2016 Wiley Periodicals, Inc. Biopolymers 105: 653-664, 2016.

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Propensities of peptides containing the Asn‐Gly segment to form β‐turn and β‐hairpin structures

Kang

Yoo

2016

Biopolymers

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“…Peptides that form β-strand mimetics are therapeutically used to inhibit proteases or proteinprotein interactions (26,27). One approach targeted amyloid fibrils by computationally designing a peptide to form a terminating β-strand on a growing fibril (28).…”

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Computational design of a symmetric homodimer using β-strand assembly

Stranges

Machius

Miley

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Computational design of novel protein-protein interfaces is a test of our understanding of protein interactions and has the potential to allow modification of cellular physiology. Methods for designing high-affinity interactions that adopt a predetermined binding mode have proved elusive, suggesting the need for new strategies that simplify the design process. A solvent-exposed backbone on a β-strand is thought of as "sticky" and β-strand pairing stabilizes many naturally occurring protein complexes. Here, we computationally redesign a monomeric protein to form a symmetric homodimer by pairing exposed β-strands to form an intermolecular β-sheet. A crystal structure of the designed complex closely matches the computational model (rmsd 1.0 Å). This work demonstrates that β-strand pairing can be used to computationally design new interactions with high accuracy.computational protein design | protein design | protein interface design | Rosetta P rotein-protein interactions and assemblies are essential for a wide array of cellular processes. The ability to rationally design unique protein interactions could provide scaffolds for functional reactions and new reagents for perturbing and monitoring cellular processes. Computational approaches for interface design have advanced rapidly in recent years and have allowed interactions to be engineered for increased affinity or altered specificity (1, 2). One long-standing goal is the creation of unique interactions. Thus far, most computational designs of new interactions have involved either the pairing of α-helices (3-6) or binding of an α-helix to an open groove on a target (7-10). Other methodologies have focused on grafting side-chain interactions from a known interaction onto another scaffold (7,11,12). There have been two examples of structurally confirmed unique computational interface designs (6, 7), however these sample a limited set of modes by which proteins can interact. New methods of constructing an interface are necessary to mimic the ways nature forms protein-protein interactions (13).There are many examples of naturally occurring protein heterodimers, homodimers, and larger complexes where β-strands from each chain associate to form an intermolecular β-sheet (14); β-strand pairing has also been observed in evolved antibody-antigen interactions (15) and monobody-target interfaces selected from phage display libraries (16). It has been proposed that β-strand pairing is so favorable that naturally occurring proteins often use negative design to avoid edge-to-edge association. In one study, 75 monomeric β-sheet proteins were visually examined to see if they contained structural features that would be predicted to disfavor β-sheet formation across their edge strands (17). In almost every case, one or more negative design elements were present including prolines, strategically placed charges, very short edge strands, loop coverage, and irregular edge strands. The propensity of exposed β-strands to pair is reinforced by observations of intermolecular β-sheet forma...

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“…The resulting type I conjugates form an intramolecularly hydrogen-bonded (IHB) U-turn, which induces an artificial parallel β sheet (Scheme 1). [7][8][9][10] A large number of ferrocene-peptide bioconjugates have been prepared to induce ordered conformations of peptides and to develop new biomaterials. A lot of work has been devoted to ferrocene-peptide conjugates and the results have been summarised in recent reviews and monographs.…”

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confidence: 99%

C₂‐Symmetric Ferrocene–Bis(ureido)peptides: Synthesis, Conformation and Solid‐State Structure

et al. 2009

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The extension of peptide derivatives of ferrocene-1,1Ј-dicarboxylic acid by formal insertion of NH units between ferrocene and peptide strands results in ferrocene-bis(ureido)-peptides. Experimentally, alanine and dialanine methyl esters were attached to the 1-and 1Ј-position of 1,1Ј-diisocyanoferrocene to give the corresponding bis(ureido)peptide derivatives 3 and 4. The conformation of 3 has been deter-

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Artificial β-sheets: chemical models of β-sheets

Cited by 75 publications

References 56 publications

Propensities of peptides containing the Asn‐Gly segment to form β‐turn and β‐hairpin structures

Propensities of peptides containing the Asn‐Gly segment to form β‐turn and β‐hairpin structures

Computational design of a symmetric homodimer using β-strand assembly

C₂‐Symmetric Ferrocene–Bis(ureido)peptides: Synthesis, Conformation and Solid‐State Structure

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Artificial β-sheets: chemical models of β-sheets

Cited by 75 publications

References 56 publications

Propensities of peptides containing the Asn‐Gly segment to form β‐turn and β‐hairpin structures

Propensities of peptides containing the Asn‐Gly segment to form β‐turn and β‐hairpin structures

Computational design of a symmetric homodimer using β-strand assembly

C2‐Symmetric Ferrocene–Bis(ureido)peptides: Synthesis, Conformation and Solid‐State Structure

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C₂‐Symmetric Ferrocene–Bis(ureido)peptides: Synthesis, Conformation and Solid‐State Structure