total synthesis of nisin by solid phase peptide synthesis solid-phase synthesis of nisin lipopeptide analogues - total-synthesis-of-nisin-solid-phase-peptide-synthesis Nisin Advancing Antimicrobial Research: The Total Synthesis of Nisin via Solid-Phase Peptide Synthesis

where-are-natriuretic-peptides-produced The total synthesis of nisin has long been a significant goal in the field of peptide chemistry, particularly due to nisin's potent antimicrobial properties and its classification as a lantibiotic. Recent advancements have increasingly leveraged solid-phase peptide synthesis (SPPS) as a primary methodology for achieving this complex objective, enabling the creation of nisin and its various analogues.作者：SN Mthembu·2022·被引用次数：13—Thesolid-phase synthesisof C-terminal Cyspeptideacids is problematic because it is accompanied by a side reaction, namely, the abstraction ... This approach facilitates detailed studies into nisin's structure-activity relationships and the development of novel antimicrobial agents.What is solid phase peptide synthesis?

Nisin, a naturally occurring bacteriocin, is a ribosomally synthesized and post-translationally modified peptide (RiPP) that exhibits broad-spectrum activity against Gram-positive bacteria. Its unique structure, characterized by multiple thioether-containing rings and unusual amino acids like dehydroalanine (Dha), presents considerable synthetic challenges. Traditional solution-phase methods for peptide synthesis are often laborious and inefficient for such complex molecules. However, solid-phase peptide synthesis (SPPS), a technique that involves assembling amino acids sequentially on a solid support, such as a resin, has emerged as a powerful tool. This method allows for easier purification of intermediates and a more streamlined synthetic process, making the total synthesis of nisin and its derivatives more tractable.

Researchers have explored various strategies within the SPPS framework to achieve the total synthesis of nisin. For instance, the total synthesis of nisin by the Shiba group utilized a desulfurisation approach to construct the characteristic lanthionine bridges, followed by the condensation of peptide fragments. More contemporary approaches, such as those employing Fmoc-SPPS techniques, have been instrumental in synthesizing on-resin lipopeptide analogues of nisin A.作者：K Manzor·2017·被引用次数：9—A number of A-ring analogues of the lantibioticnisin, containing replacements for the Dha at position 5, have been successfully prepared bysolid-phase peptide... These studies aim to investigate the structure-activity relationships of nisin, particularly concerning its interaction with Lipid II, a crucial component of bacterial cell membranes. The ability to synthesize specific fragments, such as the A-ring fragment of the lantibiotic nisin, or even individual ring structures like ring A and B structures from nisin, is a testament to the precision offered by solid-phase peptide synthesis.

The synthesis of nisin analogues often involves addressing the unique modifications present in the natural peptide. For example, replacements for the dehydroalanine (Dha) residue at specific positions have been successfully prepared using SPPS. Furthermore, the incorporation of non-natural amino acids or modifications, such as thioamide links, has also been achieved through solid-phase peptide synthesis of analogues of the N-terminus A-ring fragment of the lantibiotic nisin. This flexibility is crucial for generating diverse libraries of nisin variants for screening and optimization. The development of strategies for the solid-phase synthesis of nisin lipopeptide analogues using orthogonally protected lanthionines synthesized by ring-opening chemistry exemplifies the sophisticated methodologies being employed.

The efficacy of SPPS in producing complex peptides is further highlighted by its application in the total synthesis of the lantibiotic lactocin S, another member of the lantibiotic family. This underscores the broader applicability of solid-phase peptide synthesis for constructing a range of related compounds. The growing body of research utilizing solid-phase peptide synthesis for nisin and its analogues contributes significantly to our understanding of peptide chemistry and the development of new therapeutic agents. The ability to perform peptide synthesis with high fidelity on a solid support allows for the exploration of novel chemical space, paving the way for next-generation antimicrobials.https://ualberta.scholaris.ca/server/api/core/bits... The ongoing efforts in peptide synthesis are critical for both fundamental research and the potential translation of these findings into clinical applications, ultimately contributing to the fight against antibiotic resistance.