Design of Secondary Structures in Unnatural Peptides: Stable Helical γ-Tetra-, Hexa-, and Octapeptides and Consequences of α-Substitution

Hanessian, Stephen; Luo, Xi; Schaum, and Robert; Michnick, Stephen W.

doi:10.1021/ja9814671

Cited by 292 publications

(189 citation statements)

References 19 publications

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“…The folded conformation of 2a also persisted in the presence of the highly polar solvent DMSO-d 6 , which is known to denature many biological macromolecules. As shown in Fig.…”

Section: Resultsmentioning

confidence: 97%

“…In recent years there has been intense interest in developing folding oligomers and polymers (foldamers) with unnatural backbones that adopt well-defined structures (1-3), which may eventually lead to protein-like molecular objects with sizes in the nanometer range. Many foldamer systems have been described (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Despite the progress made so far, the foldamer field is still in its infancy.…”

mentioning

confidence: 99%

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Creating nanocavities of tunable sizes: Hollow helices

Gong

Zeng

Zhu

et al. 2002

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

154

100

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A general strategy for creating nanocavities with tunable sizes based on the folding of unnatural oligomers is presented. The backbones of these oligomers are rigidified by localized, three-center intramolecular hydrogen bonds, which lead to well-defined hollow helical conformations. Changing the curvature of the oligomer backbone leads to the adjustment of the interior cavity size. Helices with interior cavities of 10 Å to >30 Å across, the largest thus far formed by the folding of unnatural foldamers, are generated. Cavities of these sizes are usually seen at the tertiary and quaternary structural levels of proteins. The ability to tune molecular dimensions without altering the underlying topology is seen in few natural and unnatural foldamer systems

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“…The folded conformation of 2a also persisted in the presence of the highly polar solvent DMSO-d 6 , which is known to denature many biological macromolecules. As shown in Fig.…”

Section: Resultsmentioning

confidence: 97%

mentioning

confidence: 99%

Creating nanocavities of tunable sizes: Hollow helices

Gong

Zeng

Zhu

et al. 2002

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

154

100

View full text Add to dashboard Cite

show abstract

“…Similarly in b-and the higher u-amino acid residues rotational restrictions about the flanking single bonds may be anticipated upon substitution at a specific position. The extensive literature on structure formation in peptides containing multiply substituted b-and g-residues clearly illustrates the role of substituent effects (Hanessian et al 1998;Rueping et al 2002;Seebach et al 2004). For example, Seebach and co-workers have established the effectiveness of a-, b-, g-trisubstituted g-amino acids in promoting folded structures in short sequences (Brenner & Seebach 2001;Seebach et al 2001a).…”

Section: Stereochemically Constrained U-amino Acids In Peptide Designmentioning

confidence: 99%

Expanding the polypeptide backbone: hydrogen-bonded conformations in hybrid polypeptides containing the higher homologues of α-amino acids

Chatterjee

Roy

Balaram

2007

J. R. Soc. Interface.

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Half a century has passed since the hydrogen-bonded secondary structures of polypeptides and proteins were first recognized. An extraordinary wealth of conformational information is now available on peptides and proteins, which are formed of a-amino acid residues. More recently, the discovery of well-folded structures in oligopeptides containing b-amino acids has focused a great deal of current interest on the conformational properties of peptides constructed from higher homologues (u) of a-amino acids. This review examines the nature of intramolecularly hydrogen-bonded conformations of hybrid peptides formed by amino acid residues, with a varying number of backbone atoms. The b-turn, a ubiquitous structural feature formed by two residue (aa) segments in proteins and peptides, is stabilized by a 10-atom (C 10 ) intramolecular 4/1 hydrogen bond. Hybrid turns may be classified by comparison with their aa counterparts. The available crystallographic information on hydrogen-bonded hybrid turns is surveyed in this review. Several recent examples demonstrate that individual u-amino acid residues and hybrid dipeptide segments may be incorporated into the regular structures of a-peptides. Examples of both peptide helices and hairpins are presented. The present review explores the relationships between folded conformations in hybrid sequences and their counterparts in all a-residue sequences. The use of stereochemically constrained u-residues promises to expand the range of peptide design strategies to include u-amino acids. This approach is exemplified by well-folded structures like the C 12 (ag) and C 14 (gg) helices formed in short peptides containing multiply substituted g-residues. The achiral g-residue gabapentin is a readily accessible building block in the design of peptides containing g-amino acids. The construction of globular polypeptide structures using diverse hybrid sequences appears to be a realistic possibility.

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“…These observations encouraged us to investigate the larger octa peptides. 3 . Like the peptides studied earlier, Aba3 and Aba6 were found to take an extended structure.…”

Section: Peptides 2 Andmentioning

confidence: 99%

“…3,4 Recent capability of designing β-hairpins, 5 enabled studies of hybrid peptides containing α-and β amino acids. 6 It has been observed that the inclusion of β-amino amino acids is tolerated without disrupting the same side of an extended sheet, which may enable the residue to participate in H-bonding simultaneously.…”

mentioning

confidence: 99%

β-Hairpin peptides containing 3-amino benzoic acid, a constrained γ-amino acid

Rao¹,

Kumar²,

Kunwar³

2005

Arkivoc

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Dedicated to Prof. P. T. Narasimhan on the occasion of hisAbstract β-Hairpin consists of two β-strands joined by an appropriate di-peptide loop. In the designed hairpin the strands consist of hydrophobic residues, while the turn is a β-turn, invariably consisting of Pro-Gly residues. Incorporation of 3-aminobenzoic acid (Aba) in the β-hairpin peptides does not compromise the stability of the secondary structure. Unlike some of the designs, these hairpins permit accommodation of both enantiomers of Pro-Gly turn motifs. Formation of β-hairpin with L Pro in the turn region is unique, which is generally not favoured due the incompatible twist constraints arising in natural amino acids. We have also found that these strands can accommodatePro and achiral Aib-Aib turn motifs in the hairpin. These results point to the dampening of the twist in the strands due to the presence of Aba.

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Design of Secondary Structures in Unnatural Peptides: Stable Helical γ-Tetra-, Hexa-, and Octapeptides and Consequences of α-Substitution

Cited by 292 publications

References 19 publications

Creating nanocavities of tunable sizes: Hollow helices

Creating nanocavities of tunable sizes: Hollow helices

Expanding the polypeptide backbone: hydrogen-bonded conformations in hybrid polypeptides containing the higher homologues of α-amino acids

β-Hairpin peptides containing 3-amino benzoic acid, a constrained γ-amino acid

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