Efficient α‐Helix Induction in a Linear Peptide Chain by <i>N</i>‐Capping with a Bridged‐tricyclic Diproline Analogue

Hack, Verena; Reuter, Cédric; Opitz, Robert; Schmieder, Peter; Beyermann, Michael; Neudörfl, Jörg‐Martin; Kühne, Ronald; Schmalz, Hans‐Günther

doi:10.1002/anie.201302014

Cited by 35 publications

(35 citation statements)

References 50 publications

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“…This in‐depth investigation was not restricted only to simple amino acid derivatives but, although in a limited number of cases, expanded to short peptides as well. In this connection, X‐ray diffraction analyses were carried out on Mpr dipeptides and tripeptides, with the methyl group at position C3 (3‐Mpr) , on a homo‐dipeptide with a vinyl group (Vpr) at C4 , and on dipeptides with a 4,5‐difluoromethane (4,5‐Dfmp) or a 5,5‐dimethyl (5,5‐Dmp) substituent.…”

Section: Introductionmentioning

confidence: 99%

Handedness preference and switching of peptide helices. Part I: Helices based on protein amino acids

Crisma

Zotti

Formaggio³

et al. 2014

J. Pept. Sci.

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In this article, we review the relevant results obtained during almost 60 years of research on a specific aspect of stereochemistry, namely handedness preference and switches between right-handed and left-handed helical peptide structures generated by protein amino acids or appropriately designed, side-chain modified analogs. In particular, we present and discuss here experimental and theoretical data on three categories of those screw-sense issues: (i) right-handed/left-handed α-helix transitions underwent by peptides rich in Asp, specific Asp β-esters, and Asn; (ii) comparison of the preferred conformations adopted by helical host-guest peptide series, each characterized by an amino acid residue (e.g. Ile or its diastereomer aIle) endowed with two chiral centers in its chemical structure; and (iii) right-handed (type I)/left-handed (type II) poly-(Pro)n helix transitions monitored for peptides rich in Pro itself or its analogs with a pyrrolidine ring substitution, particularly at the biologically important position 4. The unique modular and chiral properties of peptides, combined with their relatively easy synthesis, the chance to shape them into the desired conformation, and the enormous chemical diversity of their coded and non-coded α-amino acid building blocks, offer a huge opportunity to structural chemists for applications to bioscience and nanoscience problems.

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Section: Introductionmentioning

confidence: 99%

Handedness preference and switching of peptide helices. Part I: Helices based on protein amino acids

Crisma

Zotti

Formaggio³

et al. 2014

J. Pept. Sci.

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show abstract

“…The Pro-Pro dipeptide segment forms a partial helical structure by two intramolecular hydrogen bonds [71] and might be used to nucleate helical folding [72,73]. Based on Kemp's Pro-Pro derivative designed to function as an α-helix-inducing N-cap motif [74,75], the groups of Kühne and Schmalz [41] designed a tricyclic diproline scaffold 48 for efficient α-helix induction in a linear peptide, as shown in Scheme 10.…”

Section: Stabilization Of α-Helices and β-Turns In Peptidesmentioning

confidence: 98%

“…Of special interest are type IIc cyclic constraints since they constitute potent type II β-turn-inducing molecular scaffolds [37]. In this context it is important to mention the contributions of the Moeller [38], respectively, Wagner [39] and Schmalz groups since they showed that stereo-and regiospecific functionalization of the proline ring with suitable alkene moieties is a powerful tool to define the conformation of the fused pyrrolidine ring as polyproline type II (PPII) helix mimic [40] or as an α-helix-nucleating motif [41] to stabilize the secondary structure of relatively small peptide sequences (vide infra).…”

Section: Secondary Structure-inducing Peptide Mimetic Scaffolds Synthmentioning

confidence: 99%

“…As a control peptide, the tricyclic Pro-Pro dipeptide was replaced by Pro-Pro, and both peptides were analyzed by circular dichroism on their helical content. It turned out that the Pro-Pro control peptide was random coiled (conformationally unordered), while peptide 52 adopted a high degree of α-helical character [41].…”

Section: Stabilization Of α-Helices and β-Turns In Peptidesmentioning

confidence: 99%

“…Substituted isophthalamides emerged as early lead structures that were investigated for the inhibition of β-secretase, the enzyme responsible for releasing the neurotoxic peptide fragment Aβ [40][41][42] by processing the amyloid precursor protein.…”

Section: Rcm For the Synthesis Of Bioactive Peptides And Peptidomimeticsmentioning

confidence: 99%

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Synthesis of Cyclic Peptides and Peptidomimetics by Metathesis Reactions

Rijkers

2015

Topics in Heterocyclic Chemistry

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This review surveys developments in the field of ring-closing metathesis and cross-metathesis reactions applied to the synthesis of constrained amino acids, peptides, and peptidomimetics. Examples, in which metathesis is used as one of the synthetic tools to arrive at the desired peptide molecules as well as examples that describe in-depth optimized metathesis protocols, will be discussed. Currently, metathesis reactions are well-accepted synthetic tools within the field of peptide chemistry and provide peptides unprecedented properties like conformational, metabolic, and chemical stability and improved bioactivity.

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Construction of Constrained Helices

2021

Cyclized Helical Peptides

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Efficient α‐Helix Induction in a Linear Peptide Chain by N‐Capping with a Bridged‐tricyclic Diproline Analogue

Cited by 35 publications

References 50 publications

Handedness preference and switching of peptide helices. Part I: Helices based on protein amino acids

Handedness preference and switching of peptide helices. Part I: Helices based on protein amino acids

Synthesis of Cyclic Peptides and Peptidomimetics by Metathesis Reactions

Construction of Constrained Helices

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