total synthesis mersacidin solid-phase peptide total - nextech-labs-peptides peptide The Total Synthesis of Mersacidin: Advancing Antimicrobial Peptide Research Through Solid-Phase Peptide Synthesis

peptide-therapy-montvale The intricate world of antimicrobial peptides has seen a surge in interest, particularly with the emergence of compounds like mersacidin.The role of chemical synthesis in developing RiPP antibiotics Mersacidin, a potent lantibiotic produced by *Bacillus* species, exhibits significant activity against a broad spectrum of Gram-positive bacteria by targeting cell-wall biosynthesis. The total synthesis of such complex molecules is crucial for understanding their structure-activity relationships, developing novel analogs, and potentially overcoming antibiotic resistance. This article delves into the methodologies employed for the total synthesis of mersacidin, with a particular focus on the application of solid-phase peptide synthesis (SPPS), a cornerstone technique in modern peptide synthesis.

Mersacidin is characterized by its unique structure, featuring a 20-amino acid sequence that includes post-translational modifications such as lanthionine rings. These modified amino acids, particularly the presence of lanthionine-containing peptides, contribute to its stability and antimicrobial efficacy. The total synthesis of mersacidin presents a considerable challenge due to these complex modifications and the need for precise stereochemical control.作者：B Mothia·2012·被引用次数：2—...peptidebysolid phase peptide synthesis. Teoc and TMSE deprotection was ...total peptideproduced. 53. However fully modified nisin was produced when ...

The development of solid-phase peptide synthesis (SPPS) has revolutionized the field of peptide synthesis.作者：L Lepsa·2000·被引用次数：271—2 Illustration of the development approach for Atosiban drug substance, utilizing a common intermediate for solution- andsolid-phasesyntheses. 236. Andersson ... This technique, pioneered by RTotal Synthesis of Malacidin A by β-Hydroxy Aspartic Acid .... Bruce Merrifield, involves the sequential addition of amino acids to a growing peptide chain anchored to an insoluble solid support, often a resin.Mersacidinis defined as a subtype of lantibiotic synthesized by bacillus species, which acts against multiple Gram-positive bacteria by disrupting cell-wall ... This approach offers several advantages over traditional solution-phase methods, including simplified purification of intermediates, automation capabilities, and the ability to synthesize longer and more complex peptides. For the total synthesis of mersacidin, SPPS provides a robust framework for assembling the linear peptide precursor.作者：EL Ongey·2016·被引用次数：137—...solid-phase peptidesynthesis;. VRE: vancomycin resistant Enterococci. ...Total synthesisofpeptideantibiotic nisin. Tetrahe- dron Lett ...

Strategies for solid-phase peptide synthesis of mersacidin and related lantibiotics often employ protecting group chemistries such as Fmoc (9-fluorenylmethyloxycarbonyl) or Boc (tert-butyloxycarbonyl)作者：T Denoël·2014—2.3.4Synthesisfrom dehydroalanine. An orthogonally protected Lan suitable forsolid phase peptide synthesis(SPPS) was synthesized by Probert et al. to .... The Fmoc-based solid-phase peptide synthesis (SPPS) is particularly popular due to the mild conditions required for deprotection, which are compatible with sensitive amino acid side chains and the peptide backbone.Versatile and Stereoselective Syntheses of Orthogonally ... The process typically involves repeated cycles of:

1. Deprotection: Removal of the N-terminal protecting group of the resin-bound amino acid.AI. The research details thetotal synthesisof the lantibiotic lactocin S, a naturalpeptidefrom Lactobacillus sakei, throughsolid-phase peptidecyclizations ...

2. Coupling: Activation of the next incoming amino acid and its subsequent attachment to the deprotected N-terminus.

3. Washing: Removal of excess reagents and byproductsSolid-phase peptide synthesis: from standard procedures ....

This iterative process allows for the step-by-step construction of the precise amino acid sequence of mersacidin. The incorporation of non-standard amino acids and the formation of thioether linkages, characteristic of lanthionine-containing peptides, require specialized reagents and carefully optimized reaction conditions within the solid-phase peptide synthesis frameworkMS of E17A mersacidin (expected mass, 1767.2 Da) (A) .... Researchers have explored various methods for introducing these modified residues, including the synthesis of orthogonally protected lanthionine derivatives suitable for solid-phase peptide synthesis.

Beyond the linear assembly, the formation of the characteristic lanthionine rings is a critical step in the total synthesis of mersacidinThe role of chemical synthesis in developing RiPP antibiotics. These rings are typically formed through intramolecular Michael additions of cysteine thiols to dehydroalanine or dehydrobutyrine residues.AI. The research details thetotal synthesisof the lantibiotic lactocin S, a naturalpeptidefrom Lactobacillus sakei, throughsolid-phase peptidecyclizations ... While this can occur post-synthetically in solution, integrating these cyclization events within a solid-phase peptide synthesis strategy requires careful planning.作者：B Mothia·2012·被引用次数：2—...peptidebysolid phase peptide synthesis. Teoc and TMSE deprotection was ...total peptideproduced. 53. However fully modified nisin was produced when ... Some approaches involve cyclization on the resin, while others may involve cleaving a precursor peptide from the solid phase and performing the cyclization in solution.

The total synthesis of mersacidin and its analogs, such as malacidin A, highlights the versatility of SPPS.作者：R Dickman·2019·被引用次数：51—We have usedsolid-phase peptide synthesisto prepare individual ring A and B structures from nisin, the related lantibiotic mutacin, and synthetic analogues. For instance, the total synthesis of malacidin A has been achieved using a combination of Fmoc-based SPPS and the incorporation of $\beta$-hydroxyaspartic acid. Similarly, research into other lantibiotics like nisin and mutacin has benefited immensely from solid-phase peptide synthesis for preparing fragments and synthetic analogs. The ability to perform solid-phase peptide synthesis on a larger scale is also being investigated for the production of therapeutic peptides.

The significance of achieving the total synthesis of mersacidin extends beyond mere chemical accomplishment. It enables the production of pure, well-characterized material for detailed biological studies. This includes investigating its mechanism of action, determining its minimum inhibitory concentrations (MICs) against various bacterial strains, and exploring its potential as a therapeutic agent作者：Y Belguesmia·2024·被引用次数：4—In this study, microwave-assistedsolid-phase peptide synthesiswas used to produce the leaderless two-peptidebacteriocin enterocin DD14 (EntDD14).. Furthermore, the insights gained from the total synthesis process can guide the design of novel peptide analogs with enhanced potency, improved pharmacokinetic properties, or broader spectrum of activityEpimerisation in Peptide Synthesis. The exploration of full synthetic routes allows for the systematic modification of the mersacidin structure, leading to a deeper understanding of the relationship between its chemical structure and its biological function.

In conclusion, the total synthesis of mersacidin represents a significant advancement in the field of antimicrobial peptide research.作者：Y Belguesmia·2024·被引用次数：4—In this study, microwave-assistedsolid-phase peptide synthesiswas used to produce the leaderless two-peptidebacteriocin enterocin DD14 (EntDD14). The application of solid-phase peptide synthesis (SPPS) has proven indispensable, providing a powerful platform for the efficient and controlled assembly of this complex lantibiotic.作者：NA Santos-Filho·2015·被引用次数：57—Solid phase peptide synthesis(SPPS) was performed manually by the ... The spectra in far ultraviolet light (UV, 195–250 nm) showed that all ... Continued innovation in peptide synthesis methodologies, coupled with a deep understanding of the unique chemical features of molecules like mersacidin, will undoubtedly pave the way for the discovery and development of new therapeutic agents to combat the growing threat of bacterial infectionsEpimerisation in Peptide Synthesis. The ongoing exploration of total and phase peptide synthesis techniques continues to push the boundaries of what is achievable in peptide chemistry.23 Thetotal synthesisof nisin using a segment synthesis approach 24 and thesolid-phase peptidesynthesis of fragments and analogues of nisin [25] [26][27][28 ...