N-Triethylene glycol (N-TEG) as a surrogate for the N-methyl group: application to Sansalvamide A peptide analogs

Fernández-Llamazares, Ana I.; García, Jesús; Soto‐Cerrato, Vanessa; Pérez-Tomás, Ricardo; Spengler, Jan; Alberício, Fernando

doi:10.1039/c3cc41788c

Cited by 21 publications

(18 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a first study, they synthesized five analogs of sansalvamide A peptide bearing an N ‐triethyleneglycyl chain. Such chain was incorporated at the five different backbone positions of the parent cyclopeptide, and was found to exert similar conformational constraints as a backbone N ‐Me group, whilst providing a higher lipophilicity . Similar findings were reported for cilengitide.…”

Section: Classes Of Backbone N‐substituted Peptidessupporting

confidence: 66%

“…In several reports on the acylation of N ‐substituted peptides in solid phase, bis(trichloromethyl)carbonate (BTC) was found to be the most efficient activating reagent . This activating reagent, which is considered to convert amino acids into their corresponding acid chlorides, was introduced by Gilon et al They demonstrated that a wide range of Fmoc‐amino acids can be efficiently coupled to various functionalized N‐ alkyl peptides using BTC (Table , entry v), and reported the use of BTC in the SPPS of several N ‐backbone cyclic peptides .…”

Section: Synthetic Strategies For Backbone N‐substituted Peptidesmentioning

confidence: 99%

“…This modified coupling procedure was applied in the total SPPS of the highly N ‐methylated peptides cyclosporin O 120 and omphatolin A, both on the 2‐chlorotrityl chloride resin. Very recently, this modified procedure was also applied for the acylation of N‐ triethyleneglycyl and N‐ (4‐azidobutyl) residues bound to the 2‐chlorotrityl chloride resin (Table , entries x and xi) …”

Section: Synthetic Strategies For Backbone N‐substituted Peptidesmentioning

confidence: 99%

See 2 more Smart Citations

Review backbone N‐modified peptides: How to meet the challenge of secondary amine acylation

2015

Self Cite

View full text Add to dashboard Cite

Backbone N-substitution of peptides (N-Me and N-alkyl) has become of special interest as a chemical tool for peptide lead modification, either to improve biological activity or to optimize key pharmacokinetic characteristics. For the synthesis of backbone N-methylated peptides, many protocols have been developed already, yet some effort often has to be made to find appropriate conditions for the acylation of N-Me residues. Fewer examples are reported of peptides with other backbone N-substituents different than N-Me, and their synthesis is frequently reported as difficult. The synthesis of such peptides becomes more difficult as the size of the N-substituent increases. Coupling methods that work for the synthesis of N-methylated peptides were often found to fail when applied to peptides with larger N-substituents. This review addresses the challenges of the synthesis of backbone N-modified peptides, focusing on N-substituents larger than the N-Me group.

show abstract

Section: Classes Of Backbone N‐substituted Peptidessupporting

confidence: 66%

Section: Synthetic Strategies For Backbone N‐substituted Peptidesmentioning

confidence: 99%

Section: Synthetic Strategies For Backbone N‐substituted Peptidesmentioning

confidence: 99%

See 1 more Smart Citation

Review backbone N‐modified peptides: How to meet the challenge of secondary amine acylation

2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…All the 1-5 mer of NSAs were obtained with decent yields (Figure 3b, S5-8). There have been reports about oligo-NSGs containing skipped NSA residues 7,19,[29][30][31][32][33] but this is the first report of isolation of optically pure oligo-NSAs containing consecutive NSA residues with N-substituents other than methyl. 1H and 13C NMR spectra are shown on Figure S7 and S8.…”

Section: Synthesismentioning

confidence: 91%

A Peptoid with Extended Shape in Water

Morimoto¹,

Fukuda²,

Watanabe³

et al. 2019

Preprint

View full text Add to dashboard Cite

<div> <div> <div> <p>“Peptoids” was proposed, over decades ago, as a term describing analogs of peptides that exhibit better physicochemical and pharmacokinetic properties than peptides. Oligo-(N-substituted glycines) (oligo-NSG) was previously proposed as a peptoid due to its high proteolytic resistance and membrane permeability. However, oligo-NSG is conformationally flexible and is difficult to achieve a defined shape in water. This conformational flexibility is severely limiting biological application of oligo-NSG. Here, we propose oligo-(N-substituted alanines) (oligo-NSA) as a new peptoid that forms a defined shape in water. A synthetic method established in this study enabled the first isolation and conformational study of optically pure oligo-NSA. Computational simulations, crystallographic studies and spectroscopic analysis demonstrated the well-defined extended shape of oligo-NSA realized by backbone steric effects. The new class of peptoid achieves the constrained conformation without any assistance of N-substituents and serves as an ideal scaffold for displaying functional groups in well-defined three-dimensional space, which leads to effective biomolecular recognition. </p> </div> </div> </div>

show abstract

“…N-ethyl, 24 N-butyl, 25 and N-guanidyl butyl. 26 More recently, Albericio and coworkers have reported the synthesis of N-oligoethylene glycol (N-OEG) substituted cyclic peptides: sansalvamide A with 3 repeat units of N-OEG 27 and cilengitide with different repeat units of N-OEG such as 2, 11 and 23. 28 The synthesis of cilengitide with N-OEG 2 and sansalvamide A with N-OEG 3 by solid-phase peptide synthesis in multiple steps was reported; however, peptides with longer N-OEG substitutions were very complicated to synthesize and were reported to require extensive purification steps.…”

Section: Introductionmentioning

confidence: 99%

An alternative approach to create N-substituted cyclic dipeptides

et al. 2019

View full text Add to dashboard Cite

N-Modified peptide backbones are promising peptidomimetics which offer several advantages in terms of improved biological activity and stability. They further allow the development of novel functional materials.However, the synthesis of N-substituted peptides is very challenging with the existing methods, particularly the synthesis of peptides with larger N-substituents. In this work, we are introducing a new method to create N-polyether substituted cyclic dipeptides via anionic ring-opening polymerization (AROP). Four different cyclic dipeptides with different hydrophobic functional groups were selected to create N-substituted cyclic dipeptides. Backbone amides -NHwere deprotonated with phosphazene bases to form nucleophilic initiators. Furthermore, the effect of different phosphazene bases (tBuP 4 and tBuP 2 ) and of the addition of a Lewis acid (i-Bu 3 Al) was studied in detail towards creating N-polyether-cyclic dipeptides bearing either hydrophobic poly(butylene oxide) chains, or hydrophilic linear polyglycidol chains, thanks to the polymerization of 1,2-epoxybutane and the polymerization followed by the deprotection of t-butyl glycidyl ether monomers, respectively. Moreover, we have demonstrated the possibility of avoiding the isomerization of cyclic dipeptides during the synthesis of N-substituted analogues depending on the synthetic approach. † Electronic supplementary information (ESI) available: 1 H, 13 C, 2D-HSQC, and 2D-HMBC NMR spectra, SEC traces and MALDI-ToF spectra. An additional scheme of plausible configurations. See

show abstract

N-Triethylene glycol (N-TEG) as a surrogate for the N-methyl group: application to Sansalvamide A peptide analogs

Abstract: Here we studied the N-triethylene glycol (N-TEG) group as a surrogate for the N-Me group in Sansalvamide A peptide. The five N-TEG and N-Me analogs of this cyclic pentapeptide were synthesized, and their biological activity, lipophilicity and conformational features were compared.

Cited by 21 publications

References 19 publications

Review backbone N‐modified peptides: How to meet the challenge of secondary amine acylation

Review backbone N‐modified peptides: How to meet the challenge of secondary amine acylation

A Peptoid with Extended Shape in Water

An alternative approach to create N-substituted cyclic dipeptides

Contact Info

Product

Resources

About