Silaproline Helical Mimetics Selectively Form an All‐<i>trans</i> PPII Helix

Martin, Charlotte; Legrand, Baptiste; Lebrun, Aurélien; Berthomieu, Dorothée; Martinez, Jean; Cavelier, Florine

doi:10.1002/chem.201404820

Cited by 30 publications

(31 citation statements)

References 44 publications

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“…19, 25 Within this PPI helix all amide groups adopt cis conformations and every third residue is ≈5.4 Å apart from each other 25. The substituents at the termini and/or the proline residues affect this conformational switch 26–30. Several studies examined to which extent cis amide bonds occur within predominantly PPII‐helical oligoprolines in aqueous environments 4.…”

Section: Introductionmentioning

confidence: 99%

Shape Persistence of Polyproline II Helical Oligoprolines

Garbuio

Lewandowski

Wilhelm

et al. 2015

Chemistry A European J

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Oligoprolines are commonly used as molecular scaffolds. Past studies on the persistence length of their secondary structure, the polyproline II (PPII) helix, and on the fraction of backbone cis amide bonds have provided conflicting results. We resolved this debate by studying a series of spin-labeled proline octadecamers with EPR spectroscopy. Distance distributions between an N-terminal Gd(III) -DOTA (DOTA=1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) label and a nitroxide label at one of five evenly spaced backbone sites allowed us to discriminate between the flexibility of the PPII helix and the cis amide contributions. An upper limit of 2 % cis amide bonds per residue was found in a 7:3 (v/v) water/glycerol mixture, whereas cis amides were not observed in trifluoroethanol. Extrapolation of Monte Carlo models from the glass transition to ambient temperature predicts a persistence length of ≈3-3.5 nm in both solvents. The method is generally applicable to any type of oligomer for which the persistence length is of interest.

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Section: Introductionmentioning

confidence: 99%

Shape Persistence of Polyproline II Helical Oligoprolines

Garbuio

Lewandowski

Wilhelm

et al. 2015

Chemistry A European J

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“…Therefore, in order to design a hydrophobic P II helix, proline structure should be further decorated by more lipophilic elements. The first example was provided by Martin et al, who reported on a P II helix formed by a hydrophobic proline analogue, silaproline . Indeed, silaproline is 1.2 log P units more lipophilic than proline (in N ‐Fmoc derivatives), and this may create the driving force for the preferences towards nonpolar media.…”

Section: Discussionmentioning

confidence: 99%

“…Particularly promising are silicon‐containing amino acids, which may additionally stabilize certain secondary structures . In our opinion, the most interesting case reported to date is the “lipophilic polyproline‐II structure” constructed by Martin et al In particular, NMR investigations of an oligomeric proline analogue called silaproline (Sip, 1 , Figure ) revealed that the solution structure is dominated by the polyproline‐II (P II ) helix . The latter is a unique natural secondary structure that is not stabilized by hydrogen bonds.…”

Section: Introductionmentioning

confidence: 99%

Exploring hydrophobicity limits of polyproline helix with oligomeric octahydroindole‐2‐carboxylic acid

Kubyshkin

Budiša

2018

Journal of Peptide Science

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The polyproline-II helix is the most extended naturally occurring helical structure and is widely present in polar, exposed stretches and "unstructured" denatured regions of polypeptides. Can it be hydrophobic? In this study, we address this question using oligomeric peptides formed by a hydrophobic proline analogue, (2S,3aS,7aS)-octahydroindole-2-carboxylic acid (Oic). Previously, we found the molecular principles underlying the structural stability of the polyproline-II conformation in these oligomers, whereas the hydrophobicity of the peptide constructs remains to be examined. Therefore, we investigated the octan-1-ol/water partitioning and inclusion in detergent micelles of the oligo-Oic peptides. The results showed that the hydrophobicity is remarkably enhanced in longer oligomeric sequences, and the oligo-Oic peptides with 3 to 4 residues and higher are specific towards hydrophobic environments. This contrasts significantly to the parent oligoproline peptides, which were moderately hydrophilic. With these findings, we have demonstrated that the polyproline-II structure is compatible with nonpolar media, whereas additional manipulations of the terminal functionalities feature solubility in extremely nonpolar solvents such as hexane.

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“…A,B) [Reuter et al, ], the oligomeric Ser‐Pro dipeptide mimetic of Tremmel and Geyer[Tremmel and Geyer, ], the silaproline oligomers of Martin et al (Fig. C) [Martin et al, ] and the systematic development of PPII helix‐mimetic fragments performed by Opitz et al [].…”

Section: Receptor‐bound Conformationsmentioning

confidence: 99%

“…Sip oligomers were detected to adopt a PPII helical structure. Reproduced from Martin et al []. [Color figure can be viewed at http://wileyonlinelibrary.com]…”

Section: Receptor‐bound Conformationsmentioning

confidence: 99%

Limiting Assumptions in the Design of Peptidomimetics

Marshall

Ballante

2017

Drug Development Research

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Preclinical Research Limiting the flexibility of organic compounds to enhance their affinity and selectivity for targeting a macromolecule involved in molecular recognition has become a well-developed paradigm in medicinal chemistry. While the role of reverse-turn motifs as peptidomimetics has received the most attention, β-sheets and helices are also important motifs for protein/protein interactions. The more complicated problem of mimicking the interacting surface of noncontiguous epitopes will not be considered in this review. This limited overview focuses on efforts to use amino acid synthons as secondary-structure mimetics as well as providing examples of peptidomimetic design focused on nonpeptide synthetic chemistry in contrast. In particular, the rationale of optimal design criteria for mimicry and the many naïve violations of those criteria made in its pursuit are emphasized. Drug Dev Res 78 : 245-267, 2017. © 2017 Wiley Periodicals, Inc.

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Silaproline Helical Mimetics Selectively Form an All‐trans PPII Helix

Cited by 30 publications

References 44 publications

Shape Persistence of Polyproline II Helical Oligoprolines

Shape Persistence of Polyproline II Helical Oligoprolines

Exploring hydrophobicity limits of polyproline helix with oligomeric octahydroindole‐2‐carboxylic acid

Limiting Assumptions in the Design of Peptidomimetics

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