Preparation and determination of X-ray-crystal and NMR-solution structures of γ2,3,4-peptides

Seebàch, Dieter; Brenner, Meinrad; Rueping, Magnus; Schweizer, W. Bernd; Jaun, Bernhard

doi:10.1039/b008377l

Cited by 104 publications

(77 citation statements)

References 5 publications

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“…In hybrid peptides, an additional mode of generating molecular diversity becomes apparent. The enhanced stability of peptide bonds formed by u-amino acids to proteolysis is an important consideration in the use of backbonehomologated amino acid residues in the design of peptide mimetics Seebach et al 1998bSeebach et al , 2001bFrackenpohl et al 2001;Porter et al 2002, Gopi et al 2003Lelias & Seebach 2003;Hook et al 2004;Schmitt et al 2004). Conformational features in hybrid sequences can be established only in synthetic model peptides making the collection of structural data a slow process.…”

Section: Resultsmentioning

confidence: 99%

“…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). Figure 16 illustrates in interesting example of a hairpin conformation containing a d-amino acid (sugar amino acid) at the (iC2) position of the b-turn (Grotenberg et al 2004).…”

Section: Stereochemically Constrained U-amino Acids In Peptide Designmentioning

confidence: 99%

“…A bg segment forming a C 13 hydrogen bond has been characterized in the crystals of Boc-Leu-Aib-Val-bGly gAbu-Leu-AibVal-OMe and Boc-Leu-Aib-Val-bGly gAbu-LeuAib-Val-Alu-Leu-Aib-OMe (Karle et al 1997, table 1).This hydrogen-bonded turn is formally equivalent to a three-residue aaa C 13 -turn. Seebach et al (2001a) have established an incipient 2.6 14 (14-helix) in a protected tetrapeptide formed from 2,3,4-trisubstituted g-amino acids (figure 11, Seebach et al 2001a).The formation of the two consequtive C 14 hydrogen-bonded turn is undoubtedly promoted by the substitution pattern along the backbone (R, R, R) which promotes adoption of the gauche (C)-gauche (C) conformations about the C b -C g (q 1 ) and C a -C b (q 2 ) a Torsion angle values for Aib residue in the ab-turn is averaged over Aib residues 1, 3 and 5 and in the ba turn is averaged over the Aib residues 3, 5 and 7. Torsion angles of trans ACPC residue is averaged over residues 2, 4 and 6. b Torsion angle values for trans ACPC is averaged over residues 1 and 4, while Aib is averaged over residues 2 and 5. c Achiral peptide.…”

Section: Hydrogen-bonded Turns As Components Of Secondary Structuresmentioning

confidence: 99%

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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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Section: Resultsmentioning

confidence: 99%

Section: Stereochemically Constrained U-amino Acids In Peptide Designmentioning

confidence: 99%

Section: Hydrogen-bonded Turns As Components Of Secondary Structuresmentioning

confidence: 99%

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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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“…Figure 1). 81,82 More heavily side-chain-substituted derivatives, such as g 2,4 -and g 2,3,4 -peptides 1,83 can also fold to a 2.6 14 -helix ( Figure 12A). The conformation around both CÀ ÀC ethane bonds (NÀ ÀC g À ÀC b À ÀC a and C g À ÀC b À À C a À ÀCO) is sc in these helices.…”

Section: B-and G-peptide Secondary Structuresmentioning

confidence: 96%

Helices and other secondary structures of β‐ and γ‐peptides

Seebàch

Hook

Glättli³

2005

Biopolymers

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322

212

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The principal secondary structural motifs adopted by peptides assembled from beta-amino acid units are discussed: the 14-, 12-, 10-, 12/10-, and 8-helices, as well as the hairpin turn, extended structures, stacks, and sheets. Features that promote a particular folding propensity are outlined and illustrated by structures determined in solution (NMR) and in the solid-state (x-ray). The N-C(beta)-C(alpha)-CO dihedral angles from molecular dynamics simulations, which are indicative of a particular secondary structure, are presented. A brief description of a helix and a turn of gamma-peptides is also given.

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“…Equally as versatile for medicinal chemistry as well as research on foldamers are chiral fully substituted g-butyrolactams and g-amino acids. [24][25][26] The syntheses of chiral g-amino acids rely mostly on either chiral resolution or the use of chiral auxiliaries. [27] Direct catalytic enantioselective methods furnishing these building blocks are therefore highly desirable.…”

Section: Catalyst Screeningmentioning

confidence: 99%

Adapting to Substrate Challenges: Peptides as Catalysts for Conjugate Addition Reactions of Aldehydes to α,β‐Disubstituted Nitroolefins

Duschmalé

Wennemers

2011

Chemistry A European J

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Conjugate addition reactions of aldehydes to α,β-disubstituted nitroolefins are important because they provide synthetically useful γ-nitroaldehydes bearing three consecutive stereogenic centers. Such reactions are challenging due to the drastically lower reactivity of α,β-disubstituted nitroolefins compared to, for example, β-monosubstituted nitroolefins. The testing of a small collection of peptides of the type Pro-Pro-Xaa (Xaa=acidic amino acid) led to the identification of H-Pro-Pro-D-Gln-OH and H-Pro-Pro-Asn-OH as excellent stereoselective catalysts for this transformation. In the presence of 5 mol% of these peptides different combinations of aldehydes and α,β-disubstituted nitroolefins react readily with each other providing γ-nitroaldehydes in good yields and diastereoselectivities as well as excellent enantioselectivities. Chiral pyrrolidines as well as fully substituted γ-butyrolactams and γ-amino acids are easily accessible from the γ-nitroaldehydes. Mechanistic studies demonstrate that the configuration at all three stereogenic centers is induced by the peptidic catalysts. Only a minimal amount of products from homo-aldol reactions is observed demonstrating the high chemoselectivity of the peptidic catalysts.

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Preparation and determination of X-ray-crystal and NMR-solution structures of γ2,3,4-peptides

Abstract: Amino acids with side chains in the 2-, 3-, and 4-positions, prepared by addition of acyloxazolidinones to a nitroolefin and hydrogenation, have been coupled to gtetra-, and g-hexapeptides which are shown to form (M)-2.6 14 helices in the crystal state and in MeOH solution.

Cited by 104 publications

References 5 publications

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

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

Helices and other secondary structures of β‐ and γ‐peptides

Adapting to Substrate Challenges: Peptides as Catalysts for Conjugate Addition Reactions of Aldehydes to α,β‐Disubstituted Nitroolefins

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