The Backbone <i>N</i>-(4-Azidobutyl) Linker for the Preparation of Peptide Chimera

Fernández-Llamazares, Ana I.; García, Jesús; Adán, Jaume; Meunier, David; Mitjans, Francesc; Spengler, Jan; Alberício, Fernando

doi:10.1021/ol402150m

Cited by 13 publications

(18 citation statements)

References 21 publications

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“…[37] N-methylation can also be substituted with an N-(4-azido butyl) group to induce cis-amide bond formation. [38] The triazole group formed by click chemistry has also been utilized as a turn-inducing cis-proline mimetic. [39] Pseudo-prolines [40] and heterocycles [41] have been used to introduce turn structures into cyclic peptides.…”

Section: Cyclic Peptide Turnsmentioning

confidence: 99%

“…This includes the integrins, which are an important class of surface receptors involved in cell-cell and cell-matrix interactions. Highly potent and selective inhibitors have been developed through (37); R = AcNH (3D53 or PMX53), [44 ] R = H (3D624 or PMX205); [45] b) helix bundle of human C5a (38) showing activating C-terminus (bold); c) NMR structures (39) of peptides en route to 37. [44] Constrained Cyclic Peptides Angewandte Chemie constraining the pharmacophore sequence RGD into small cyclic peptides presenting this motif in a turn conformation.…”

Section: Cyclic Peptide Turnsmentioning

confidence: 99%

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Constraining Cyclic Peptides To Mimic Protein Structure Motifs

et al. 2014

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Many proteins exert their biological activities through small exposed surface regions called epitopes that are folded peptides of well-defined three-dimensional structures. Short synthetic peptide sequences corresponding to these bioactive protein surfaces do not form thermodynamically stable protein-like structures in water. However, short peptides can be induced to fold into protein-like bioactive conformations (strands, helices, turns) by cyclization, in conjunction with the use of other molecular constraints, that helps to fine-tune three-dimensional structure. Such constrained cyclic peptides can have protein-like biological activities and potencies, enabling their uses as biological probes and leads to therapeutics, diagnostics and vaccines. This Review highlights examples of cyclic peptides that mimic three-dimensional structures of strand, turn or helical segments of peptides and proteins, and identifies some additional restraints incorporated into natural product cyclic peptides and synthetic macrocyclic peptidomimetics that refine peptide structure and confer biological properties.

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Section: Cyclic Peptide Turnsmentioning

confidence: 99%

Section: Cyclic Peptide Turnsmentioning

confidence: 99%

Constraining Cyclic Peptides To Mimic Protein Structure Motifs

et al. 2014

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“…In another study, they synthesized an N ‐(4‐azidobutylated) analog of cilengitide, and conjugated it with a polyethylene glycol (PEG) chain through several chemical transformations. They thereby showed that the introduction of an N ‐(4‐azidobutyl) group is a valuable strategy to allow conjugation in peptides that do not have attachment sites and/or are not amenable to side‐chain modification whilst preserving biological activity . Regarding the preparation of N ‐substituted peptides through combinatorial approaches, there is one example reported.…”

Section: Classes Of Backbone N‐substituted Peptidesmentioning

confidence: 99%

“…A possible method to do so is by reductive alkylation with a suitable aldehyde (Figure , path A). Conditions for reductive N α ‐alkylation that render a high yield of N ‐monoalkylated product are reported, but they have to be optimized in each synthesis in order to minimize N,N ‐dialkylation and maintain an acceptable conversion . Another possibility to introduce the N‐ substituent is by activating the α‐amino group of the resin‐bound peptide as a sulfonamide, followed by N α ‐alkylation, and finally removal of the sulfonamide group (Figure , paths A and B).…”

Section: Synthetic Strategies For Backbone N‐substituted Peptidesmentioning

confidence: 99%

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

2015

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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.

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“…[37] Statt der N-Methylierung kann auch eine N-4-Azidobutylgruppe den gleichen Zweck erfüllen. [38] Auch die Triazolgruppe, die bei der Klick-Reaktion entsteht, induziert als Nachahmung von cis-Prolin eine Kehre. [39] Pseudoproline [40] und Heterocyclen [41] wurden ebenfalls genutzt, um Kehrenstrukturen in cyclische Peptide einzuführen.…”

Section: Cyclische Peptidkehrenunclassified

Fixierung cyclischer Peptide: Mimetika von Proteinstrukturmotiven

et al. 2014

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Viele Proteine entfalten ihre biologische Aktivität über kleine exponierte Oberflächenregionen aus gefalteten Peptiden mit wohldefinierten dreidimensionalen Strukturen, Epitope genannt. Kurze synthetische Peptidsequenzen, die diesen bioaktiven Proteinoberflächen entsprechen, bilden in Wasser keine thermodynamisch stabilen proteinähnlichen Strukturen. Die Bildung proteinähnlicher biologisch aktiver Konformationen (Stränge, Helices, Kehren) kann jedoch durch Cyclisierung in Verbindung mit anderen molekularen Verstrebungen induziert werden. Letztere helfen bei der Feinabstimmung der dreidimensionalen Struktur. Solche fixierten cyclischen Peptide können ähnliche biologische Aktivitäten und Wirkungen wie das als Vorbild dienende Protein haben, sodass sie als biologische Sonden und Leitstrukturen für Therapeutika, Diagnostika und Impfstoffe dienen können. Dieser Aufsatz beleuchtet Beispiele für cyclische Peptide, die dreidimensionale Strukturen von Strang‐, Kehren‐ oder Helixabschnitten von Peptiden und Proteinen nachahmen und beschreibt einige weitere Elemente, die in cyclisch peptidischen Naturstoffen und synthetischen makrocyclischen Peptidomimetika vorkommen, dort die Peptidstruktur verfeinern und ihr biologische Aktivitäten verleihen.

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The Backbone N-(4-Azidobutyl) Linker for the Preparation of Peptide Chimera

Cited by 13 publications

References 21 publications

Constraining Cyclic Peptides To Mimic Protein Structure Motifs

Constraining Cyclic Peptides To Mimic Protein Structure Motifs

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

Fixierung cyclischer Peptide: Mimetika von Proteinstrukturmotiven

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