All‐Thioamidated Homo‐α‐Peptides: Synthesis and Conformation

Formaggio, Fernando; Crisma, Marco; Toniolo, Claudio; Peggion, Cristina

doi:10.1002/ejoc.201300050

Cited by 12 publications

(13 citation statements)

References 90 publications

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“…In the crystal structure of the terminally protected bis ‐endothioxo Gly homo‐tripeptide (Table and Figure ), an intriguing type of 2.0 5 ‐helix is observed . The C‐terminal C 5 conformation involving Gly 3 is slightly distorted from the ϕ,ψ 180°,180° values.…”

Section: Detailed Literature Survey On Peptides Since 2012mentioning

confidence: 97%

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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: 97%

“… X‐Ray diffraction structure of Z‐Gly‐ψ[CSNH]‐Gly‐ψ[CSNH]‐Gly‐OMe (adapted from ref. ). The C 5 intramolecular H‐bonds are marked…”

Section: Detailed Literature Survey On Peptides Since 2012mentioning

confidence: 97%

The fully‐extended conformation in peptides and proteins

et al. 2018

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“…While the conformation of one of them (mixed β‐/γ‐turn) was identical to that of its oxygenated parent compound, independent of solvent (CDCl 3 , DMSO d 6 ), the other (but only in the more polar environment) exhibited two conformations generated by cis / trans isomerization about an ‐XxxPro‐ tertiary amide bond. Quite interestingly, an unanticipated TOCSY pattern was noted by Formaggio and colleagues for two terminally protected, all‐thionamidated Gly homo‐peptides (trimer and tetramer) (Figure ). Crosspeaks, although rather weak, attributable to inter ‐residue signals, were detected for these two fully‐extended compounds in CDCl 3 (it is well known that magnetization, occurring via J coupling, does not pass through different residues in an oxygenated peptide chain).…”

Section: Resultsmentioning

confidence: 92%

Endothioxopeptides: A conformational overview

et al. 2016

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Although thionamides would have been first prepared two centuries ago and their chemical and spectroscopic properties extensively investigated, only much more recently (since about 1985) a well deserved but still insufficient attention has been paid to their endothioxopeptide subfamily which nonetheless currently represents a rapidly emerging area of great scientific interest in the broader field of foldameric compounds based on biologically relevant building blocks. After two brief sections offering information on the unfortunately still limited number of endothioxopeptides discovered from natural sources but also on the impressive advancements registered in the last few years in their synthetic methods, this review article outlines the results of a detailed literature survey on the ongoing great, but not systematic, progress related to the conformational consequences generated by incorporating one (or more) thionamide group(s) into a polypeptide chain. Finally, a short discussion of the growing, but still in its infancy, class of the endoselenoxopeptide congeners is also presented.

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“…The most successful method for synthesizing thioamidated peptides employs the use of thioacylating reagents 32–34 over thionating reagents 35–37 . The preparation of thioacylating reagent of respective amino acids involves a three‐step transformation including column purification steps requiring significant cost and time to generate the individual thionated amino acid building block (Table 1).…”

Section: Introductionmentioning

confidence: 99%

“…30,31 The most successful method for synthesizing thioamidated peptides employs the use of thioacylating reagents 32-34 over thionating reagents. [35][36][37] The preparation of thioacylating reagent of respective amino acids involves a three-step transformation including column purification steps requiring significant cost and time to generate the individual thionated amino acid building block (Table 1). Thus, we sought to (i) develop a purification-free synthetic strategy to obtain all the 20 naturally occurring thionated amino acids in solution and (ii) explore the most suitable reagent for the rapid removal of Fmocgroup during solid-phase synthesis of thioamidated peptides and proteins to minimize epimerization.…”

Section: Introductionmentioning

confidence: 99%

Convenient synthesis of thioamidated peptides and proteins

Khatri

Bhat

Chatterjee

2020

Journal of Peptide Science

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The unique physicochemical properties of a thioamide bond, which is an ideal isostere of an amide bond, have not been fully exploited because of the tedious synthesis of thionated amino acid building blocks. Here, we report a purification‐free and highly efficient synthesis of thiobenzotriazolides of Fmoc‐protected and orthogonally protected 20 naturally occurring amino acids including asparagine, glutamine, and histidine. The near‐quantitative conversion to the respective thioamidated peptides on solid support demonstrates the robustness of the synthetic route. Furthermore, the unaltered incorporation efficiency of thiobenzotriazolides from their stock solution till 48 h suggests their compatibility toward automated peptide synthesis. Finally, utilizing an optimized cocktail of 2% DBU + 5% piperazine for fast Fmoc‐deprotection, we report the synthesis of a thioamidated Pin1 WW domain and thioamidated GB1 directly on solid support.

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All‐Thioamidated Homo‐α‐Peptides: Synthesis and Conformation

Cited by 12 publications

References 90 publications

The fully‐extended conformation in peptides and proteins

The fully‐extended conformation in peptides and proteins

Endothioxopeptides: A conformational overview

Convenient synthesis of thioamidated peptides and proteins

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