solid-phase-peptide-synthesis-total-synthesis-lantibiotic The dominant search intent for "solid-phase synthesis of lanthionine-containing peptides" is to understand the methodologies and challenges involved in creating peptides that incorporate the unique amino acid lanthionine using solid-phase techniques. This includes exploring different protecting group strategies, the application of this synthesis in creating complex molecules like lantibiotics, and the practical considerations for achieving successful on-resin cyclization and peptide assembly.
Here's a breakdown of the key entities and concepts:
Tier 1: Core Concepts
* Primary Keyword: solid-phase synthesis of lanthionine-containing peptides
* Key Entity: lanthionine
* Core Process: solid-phase peptide synthesis (SPPS)
* Key Application: lantibiotics
* Critical Element: orthogonal protecting groups
Tier 2: Supporting Concepts & Variations
* Related Amino Acids/Modifications: lanthionine sulfoxide, sulfamidate-containing peptides, disulfide analogs
* Specific Synthesis Strategies: on-resin cyclization, S-alkylation, biomimetic approach
* Protecting Group Chemistry: Fmoc/tBu chemistry, Boc, Allyl Methyl
* Peptide Types: lanthipeptide, dipeptide derivatives, overlapping lanthionine bridges
* Challenges/Goals: total solid phase synthesis, less sterically hindered peptides, green and efficient method
Tier 3: Less Critical / Repetitive Terms
* "containing peptides," "solid phase," "phase," "solid," "with," "peptides," "solid phase peptide," "solid-phase synthesis of sulfamidate-containing peptides," "solid-phase synthesis of new Trp(Nps)-containing dipeptide derivatives," "Synthesis of Lanthionine-Containing Peptides on Solid-Phase," "Synthesis of lanthionine-containing peptides on solid phase," "lanthionine peptides," "solid phase peptide synthesis," "peptides contain," "solid phase synthesis," "Solid," "phase," "solid-phase synthesis of the overlapping lanthionine bridges," "synthesizing lanthionine-containing peptides," "Solid phase synthesis of lanthionine peptides," "Lanthionine Peptides by S-Alkylation," "synthesis of lanthionine peptides," "solid-phase peptide synthesis (SPPS) strategy," "Synthesis of Peptides Containing Overlapping Lanthionine Bridges on the Solid Phase." (Many of these are variations or common phrases within the broader topic and do not require explicit inclusion if the core concepts are covered).
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The solid-phase synthesis of lanthionine-containing peptides represents a significant advancement in peptide chemistry, enabling the construction of complex molecules that were once challenging to access.作者：S De Luca·2018·被引用次数：17—A one-pot, high-yield procedure forsynthesizing lanthionine-containing peptideswas developed. It relies on the S-alkylation of ... Lanthionine, a unique amino acid characterized by a thioether bond linking two amino acid residues, is a key feature in many biologically active peptides, most notably the lantibiotics. Developing robust solid-phase methodologies for incorporating lanthionine allows researchers to explore the structure-activity relationships of these peptides and to synthesize novel analogues with therapeutic potential. This approach leverages the efficiency of solid-phase peptide synthesis (SPPS) while addressing the specific chemical requirements for forming the characteristic lanthionine cross-links作者：S Bregant·2005·被引用次数：101—Synthesis of Peptides Containing Overlapping Lanthionine Bridges on the Solid Phase: An Analogue of Rings D and E of the Lantibiotic Nisin. Organic Letters ....
A cornerstone of successful solid-phase synthesis of lanthionine-containing peptides is the use of orthogonally protected lanthionine building blocks. Orthogonal protection ensures that specific functional groups can be selectively deprotected and reacted at different stages of the synthesis without affecting other protected groups. For lanthionine, this typically involves protecting the amino and carboxyl termini of the precursor amino acids (often serine and cysteine or related residues) in a manner that allows for controlled cyclization. Strategies often employ Fmoc/tBu chemistry, where the Fmoc group on the N-terminus can be removed under basic conditions, while tBu-based protecting groups on side chains and the C-terminus are stable to these conditions but can be cleaved with acid. This selective deprotection is crucial for facilitating the intramolecular thioether bond formation that defines lanthionine.
The synthesis of lanthionine itself, often starting from serine and cysteine, can be achieved in solution with appropriate orthogonal protecting groups, preparing it for subsequent incorporation into a growing peptide chain on the solid support作者：JM Probert·1996·被引用次数：46—Thesynthesisof orthogonally protectedlanthionine(Boc, Fmoc, Allyl Methyl ), suitable for combinatorial andsolid phase peptidechemistry is described.. The development of such protected lanthionine derivatives, including variants like lanthionine sulfoxide, is essential for expanding the scope of peptides that can be synthesized on the solid phase作者：S De Luca·2018·被引用次数：17—A one-pot, high-yield procedure forsynthesizing lanthionine-containing peptideswas developed. It relies on the S-alkylation of ....
Forming the lanthionine thioether bridge directly on the solid support (on-resin cyclization) is a primary goal in this fieldSolid phase synthesis of lanthionine peptides - Springer Link. This strategy simplifies the overall synthetic route and allows for the direct assembly of lanthionine-containing peptides, including complex structures like lantibiotics. Several approaches have been explored:
* S-Alkylation: A common method involves the S-alkylation of a dehydroalanine (Dha) or dehydrobutyrine (Dhb) residue by a cysteine thiol on the resin作者：JP Mayer—Solid phase synthesis of lanthionine peptides. Chapter. pp 291–292; Cite this chapter. Download book PDF.. This can be achieved using various activation methods and reagents designed for efficient and stereoselective thioether bond formation.A facile method for the direct synthesis of lanthionine ... The precursor peptides are typically synthesized using standard SPPS techniques, with the Dha/Dhb residues being introduced or generated in situ, and the cysteine residues being strategically placed for cyclization.作者：S De Luca·2018·被引用次数：17—A one-pot, high-yield procedure forsynthesizing lanthionine-containing peptideswas developed. It relies on the S-alkylation of ...
* Biomimetic Approaches: Inspired by the natural biosynthesis of lantibiotics, researchers have also investigated biomimetic strategies. These often involve the post-translational modification of prepeptides, mimicking the enzymatic processes that occur in nature, but adapted for solid-phase synthesis.Synthesis of Lanthionine-Containing Peptides on Solid Phase ...
* Late-Stage Cyclization: In some protocols, the linear peptide containing the necessary precursor residues is synthesized first.an analogue of rings D and E of the lantibiotic nisin. - Abstract Following solid-phase synthesis, the peptide is cleaved from the resin, and the cyclization to form lanthionine occurs in solution. However, on-resin cyclization is generally preferred for its efficiency and ability to handle complex structures.
The development of reliable solid-phase synthesis methods for lanthionine-containing peptides has been particularly impactful for the study and production of lantibiotics. Lantibiotics are a class of ribosomally synthesized peptides characterized by multiple thioether cross-links, dehydration, and other post-translational modifications. They exhibit potent antimicrobial activity and have garnered significant interest as potential therapeutic agents.
The ability to perform the total solid phase synthesis of lantibiotics and their analogues allows for:
* Structure-Activity Relationship Studies: Synthesizing variants with modifications in the lanthionine bridges or other parts of the peptide to understand their impact on biological activity作者：PJ Knerr·2013·被引用次数：70—Here,solid-supported chemicalsynthesisenabled the totalsynthesisof the lantibiotic lacticin 481 and analoguescontainingcross-linkswithnon-native ....
* Development of Novel Antimicrobials: Creating new lantibiotic analogues that may overcome resistance mechanisms or possess improved pharmacokinetic properties.
* Access to Complex Peptide Architectures: Enabling the synthesis of peptides with intricate ring structures, such as those found in nisin, which contains overlapping lanthionine bridgesThe synthetic approach for thesynthesis of lanthionine peptidesusing preformed, selectively protected lanthionines has been pursued both onsolid phase[48] ....
Beyond lantibiotics, the methodologies developed for lanthionine-containing peptides can be applied to other peptide targets where thioether cross-links are important for structure, stability, or function. This includes research into peptide-based therapeutics, probes for biological systems, and materials science applications.
Despite significant progress, challenges remain in the solid-phase synthesis of lanthionine-containing peptides. These include:
* Steric Hindrance: The formation of lanthionine bridges can be sterically hindered, especially in complex peptides or when forming multiple cross-links.作者：R Dickman·2018—Solid-phasetechniqueswitha second orthogonally protected (methyl)lanthioninehave also been applied to the more complexsynthesisof overlapping ... This can lead to low yields or incomplete reactionsA Late-Stage Synthetic Approach to Lanthionine-Containing ....
* Stereochemical Control: Ensuring the correct stereochemistry during cyclization is crucial for maintaining the biological activity of the peptide.
* Scalability: Developing methods that are efficient enough for large-scale synthesis remains an ongoing effortA methodology for thesolid-phase synthesis of the overlapping lanthionine bridgesfound in many lantibiotics has been developed and selected deprotection ....
Future directions in this field will likely focus on developing more efficient and versatile protecting group strategies, exploring novel cyclization chemistries, and integrating these methods into automated synthesis platforms. The continued refinement of these techniques will undoubtedly unlock new possibilities for designing and synthesizing peptides with unique structural motifs and potent biological activities.
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