chemical synthesis of nisin solid-phase peptide synthesis Nisin - chronoline-peptide solid state peptide synthesis The Chemical Synthesis of Nisin via Solid-Phase Peptide Synthesis

pro-peptide-protein Nisin, a well-known bacteriocin, has garnered significant attention due to its potent antimicrobial activity, particularly against Gram-positive bacteria. Its complex structure, featuring multiple thioether linkages and unusual amino acids, presents a considerable challenge for total chemical synthesis. However, advances in solid-phase peptide synthesis (SPPS) have paved the way for the creation of nisin and its analogues, enabling detailed studies into its structure-activity relationships and the development of novel therapeutic agents. This article delves into the chemical synthesis of nisin utilizing solid-phase peptide synthesis, exploring the methodologies, challenges, and implications within the field of peptide synthesis作者：ACC Pereira·2026—Nisinexhibits two principal mechanisms of action: pore formation in the bacterial membrane and inhibition of cell wallsynthesis. Additionally,nisinhas been ....

The foundation of modern peptide synthesis largely rests on the principles of solid-phase peptide synthesis. This technique, pioneered by R. Bruce Merrifield, involves the sequential addition of amino acids to a growing peptide chain anchored to an insoluble polymer support, commonly referred to as a resin. The use of a solid support simplifies the purification process, as excess reagents and byproducts can be easily washed away after each coupling step. For the synthesis of nisin, particularly its various fragments and analogues, Fmoc-SPPS (9-fluorenylmethyloxycarbonyl) is a widely adopted strategy作者：T Wang·2013·被引用次数：35—Thesynthesisof polypeptides onsolid phasevia mediation by isonitriles is described. The acyl donor is a thioacid, which presumably reacts with the .... This approach utilizes the base-labile Fmoc group for temporary protection of the α-amino group, allowing for efficient deprotection and subsequent coupling cycles.

The complexity of nisin arises from its post-translational modifications. Specifically, the presence of dehydroamino acids like dehydroalanine and the formation of thioether bridges are critical for its biological activity. The chemical synthesis of these modified residues requires specialized chemistries.作者：DB Engelhardt·2022·被引用次数：5—Three lipopeptide analogues of the lantibioticnisinA have been synthesised on-resinusing Fmoc-SPPS techniques to investigate the structure–activity ... For instance, the introduction of thioether rings, such as those found in nisin rings A and B, necessitates careful planning and execution of cyclization reactions on the solid phaseIn order to elucidate the relationships between amino acid sequence and conformation of this bicyclicpeptidefragment, we have usedsolid‐phase peptide.... Researchers have explored various strategies to achieve these intricate modifications, including the use of specific coupling reagents and controlled reaction conditions作者：JC Slootweg·2013—...nisin-like structures via (chemical)synthesis. In the first part of ... Furthermore, through solution andsolid phase peptide synthesis....

Several studies have demonstrated the successful application of solid-phase peptide synthesis in creating nisin fragments and analoguesLipidated variants of the antimicrobial peptide nisin .... For example, the synthesis of nisin(1-12) and its derivatives, where dehydro residues are replaced, has been achieved using SPPS....Peptide Nisinby Protein Engineering HARRY S. ROLLEMA,* OSCAR P. KUIPERS, PAULA BOTH, WILLEM M. DE VOS, AND ROLAND J. SIEZEN Department of BiophysicalChemistry... This allows for the investigation of the role of these specific residues in the overall structure and function of the peptide.作者：M Musiejuk·2023·被引用次数：20—...nisinanalogs—protein engineering andchemicalfunctionalization of this ...nisinand mutacin rings A and B performed bysolid state peptide synthesis. Furthermore, the synthesis of A-ring analogues of nisin has been reported, highlighting the capability of SPPS to construct specific structural motifs作者：R Dickman·2019·被引用次数：50—We have usedsolid-phase peptide synthesisto prepare individual ring A and B structures fromnisin, the related lantibiotic mutacin, and synthetic analogues..

The chemical synthesis of nisin also extends to the preparation of lipopeptide analogues.作者：DB Engelhardt·2022·被引用次数：5—Three lipopeptide analogues of the lantibioticnisinA have been synthesised on-resinusing Fmoc-SPPS techniques to investigate the structure–activity ... These modifications, where a lipid moiety is attached to the peptide, can influence its pharmacokinetic properties and membrane interactions.In organicchemistry,peptide synthesisis the production of peptides, compounds where multiple amino acids are linked via amide bonds, also known as ... Techniques like Fmoc-SPPS have been employed to synthesize these lipidated variants of the antimicrobial peptide nisin, often involving the attachment of the lipid tail to the C-terminal residue or hydroxyl-containing amino acids through chemical synthesisIn organicchemistry,peptide synthesisis the production of peptides, compounds where multiple amino acids are linked via amide bonds, also known as ....

Beyond the direct synthesis of nisin, solid-phase peptide synthesis serves as a powerful tool for generating related lantibiotics and their analogues, such as mutacin and lactocin S. The ability to systematically modify amino acid sequences and introduce specific structural features allows for a deeper understanding of the lantibiotic class as a whole. This includes investigating the molecular recognition of key targets like Lipid II, a crucial precursor in bacterial cell wall biosynthesis, which is known to be bound by lantibiotics like nisin.

While solid-phase peptide synthesis offers significant advantages, the synthesis of complex peptides like nisin is not without its challenges. Incomplete coupling, side reactions, and difficulties in cleaving the peptide from the resin can impact yield and purity.作者：PJ Knerr·2012·被引用次数：91—(9) The successful construction of lactocin S (10) and both peptides of lacticin 3147 (11) bysolid-phase peptide synthesis(SPPS) highlight the ... Advanced techniques, including microwave-enhanced solid-phase peptide synthesis, have been employed to accelerate reaction times and improve coupling efficiencies. Furthermore, the development of specialized resins, amino acid derivatives, and coupling reagents continues to push the boundaries of what is achievable in peptide synthesis.

In conclusion, the chemical synthesis of nisin via solid-phase peptide synthesis represents a significant achievement in the field of Chemistry. The meticulous application of SPPS methodologies, coupled with innovative chemical strategies, enables the construction of this complex antimicrobial peptide and its various analogues.Molecular Recognition of Lipid II by Lantibiotics: Synthesis ... This capability is invaluable for elucidating the mechanisms of action of nisin, exploring its therapeutic potential, and advancing our understanding of peptide synthesis as a whole.Semi-synthesis of nisin-based peptide antibiotics - DSpace The ongoing research in this area promises further development in the engineering of Nisin and the creation of novel peptide-based antimicrobials.