Synthesis of Aib-containing cyclopeptides via the ‘azirine/oxazolone method’

Dannecker-Dörig, Ingeborg; Linden, Anthony; Heimgartner, Heinz

doi:10.1135/cccc2009017

Cited by 16 publications

(9 citation statements)

References 90 publications

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“…Among the C α ‐tetrasubstituted α‐amino acids the simplest and most common Aib was identified in the C 5 conformation only very rarely before 2012, despite the huge number of its derivative and peptide X‐ray diffraction structures solved. It is worth recalling that this secondary structure was found sterically and energetically allowed for Aib, although much less favored than the helical conformations (for a specific review article on this topic, see ref.…”

Section: Detailed Literature Survey On Peptides Since 2012mentioning

confidence: 99%

The fully‐extended conformation in peptides and proteins

et al. 2018

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The intramolecularly H‐bonded, fully‐extended conformation (C5) of an α‐amino acid residue (and the resulting 2.05‐helix obtained via its propagation) is one of the least extensively investigated types of peptide and protein backbone secondary structure. This situation does still currently occur despite its unique ability to enjoy by far the largest separation per residue among peptide conformations. In this article, we offer a detailed update of our present knowledge on this intriguing 3D‐structure of peptides in the crystal state as obtained from recently published investigations, complemented by a statistical analysis for its occurrence in the crystal structures of α‐amino acid derivatives and peptides available in the Cambridge Structural Database. We have expanded this useful information to the results of a bioinformatics analysis performed on this (so far largely unappreciated) conformation authenticated in all proteins solved by X‐ray diffraction to a resolution of ≤ 1.5 Å. In the last section, we describe the results of our DFT calculations on the conformational preferences of a set of homopeptides (from monomer to octamer) based on as many as six proteins and two noncoded, carefully selected, α‐amino acids. From this literature survey integrated by new energy calculations, we have definitely provided strong support to the thesis that this polypeptide 3D‐structure does indeed exist, it should be not neglected in future studies by structural biochemists, and it represents a very attractive, novel backbone for applications for organic, medicinal, and biomaterials chemists.

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Section: Detailed Literature Survey On Peptides Since 2012mentioning

confidence: 99%

The fully‐extended conformation in peptides and proteins

et al. 2018

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“…This scenario changed drastically when X‐ray diffraction crystallography began to be extensively applied to cyclopeptides. In our search, including the Cambridge Crystallographic Database (CSD version 5.36, updated to November 2014, organics only) by using a generic tripeptide backbone as the search fragment and the criteria N(1)…O(3) 2.5–3.6 Å and H(1)…O(3) 1.5–2.7 Å, 14 examples of ɛ‐turns in cyclopeptides were identified: one in a cyclotetra‐, 11 in cyclopenta‐ (including one cyclodepsi), and two in cyclohexapeptides (Table ) . Only one tertiary amide bond (entry 10 in Table ), internal to the ɛ‐turn, is disposed in the cis conformation (the related ω 1 Gly‐Pro bond has a value of −8.2°).…”

Section: Literature Survey On Peptidesmentioning

confidence: 99%

Intramolecular backbone···backbone hydrogen bonds in polypeptide conformations. The other way around: ɛ‐turn

et al. 2017

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In this study, we performed a detailed literature survey of the ɛ-turn in peptides and proteins. This three-dimensional structural feature is characterized by an eleven-membered pseudo-cycle closed by an intramolecular backbone…backbone H-bond. Interestingly, in this motif the direction of the N-H…O = C H-bond runs opposite to that of the much more popular and extensively investigated α-, β-, and γ-turns. We did not authenticate unequivocally the ɛ-turn main-chain reversal topology in any linear short peptide. However, it is frequently observed in small cyclic peptides formed by four, five, and six amino acid residues with stringent geometric requirements. Rather surprisingly, ɛ-turns do occur in proteins, although to a relatively moderate extent, as an isolated feature or in the turn segment of hairpin motifs based on two antiparallel, pleated β-strands. Moreover, the ɛ-turn may also host not only the seven-membered, intramolecularly H-bonded, pseudo-cycle termed γ-turn, either of the classic or inverse type, but also one (or even two) cis peptide bond(s) or a β-bulge conformation. Based on their ϕ, ψ backbone torsion angles, we were able to classify the protein ɛ-turns in six different families. Conformational energy computations using the DFT methodology were also performed on the ɛ-turns adopted by the amino acid triplet -Gly-Gly-Gly- (Gly is the most commonly found residue at each of the three positions in our analysis of proteins). Again, in this computational study, six families of turns were identified, but only some of them resemble rather closely those extracted from our investigation on proteins.

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“…As shown in previous studies [7][8][25] [37], the coupling of two α,α-disubstituted α-amino acids does not suffer from steric hindrance. This is of importance because coupling reactions with N-terminal Aib residues are known to be difficult (see e.g.…”

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confidence: 56%

Synthesis of Z‐Protected Aib‐ and Phe(2Me)‐Containing Pentapeptides and Their Crystal Structures

Arnhold

Linden

Heimgartner

2014

Helvetica Chimica Acta

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A series of pentapeptide derivatives containing alpha,alpha-disubstituted alpha-amino acids have been prepared by a combination of the 'azirine/oxazolone method' and segment condensations. X-Ray crystal-structure determinations of the molecular structures confirmed the presence of helical conformations stabilized by beta-turns of type III or III'. Pentapeptides containing (R)-Phe(2Me) form a right-handed helix, whereas those containing (S)-Phe(2Me) adopt a left-handed helical structure.

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Synthesis of Aib-containing cyclopeptides via the ‘azirine/oxazolone method’

Cited by 16 publications

References 90 publications

The fully‐extended conformation in peptides and proteins

The fully‐extended conformation in peptides and proteins

Intramolecular backbone···backbone hydrogen bonds in polypeptide conformations. The other way around: ɛ‐turn

Synthesis of Z‐Protected Aib‐ and Phe(2Me)‐Containing Pentapeptides and Their Crystal Structures

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