total chemical synthesis nisin solid-phase peptide synthesis SPPS is a method used to create peptides - total-chemical-synthesis-epidermin-solid-phase-peptide-synthesis phase peptide synthesis Advancing Nisin Research: The Role of Total Chemical Synthesis and Solid-Phase Peptide Synthesis

tosowoong-pink-peptide-12-pdrn-serum The total chemical synthesis of complex biomolecules like nisin, a potent antibacterial peptide, represents a significant frontier in scientific research. While nisin is naturally produced by *Lactococcus lactis*, its intricate structure, characterized by modified amino acids and thioether bridges (lanthionine), presents considerable challenges for laboratory replication作者：R Rink·2007·被引用次数：205—Nisindisplays four different activities: (i) it autoinduces its ownsynthesis; (ii) it inhibits the growth of target bacteria by membrane pore formation; (iii) .... This is where advanced synthetic methodologies, particularly solid-phase peptide synthesis (SPPS), become crucial. SPPS offers a powerful platform for constructing nisin and its analogues, enabling a deeper understanding of its structure-activity relationships and unlocking its potential for therapeutic and biotechnological applications.

The Challenge and Promise of Nisin Synthesis

Nisin belongs to the lantibiotic class of peptides, distinguished by the presence of lanthionine rings formed through post-translational modification of specific amino acid residues. This unique structural feature contributes to its broad-spectrum antibacterial activity, primarily against Gram-positive bacteria, by targeting lipid II, a precursor in cell wall biosynthesis.Lanthipeptides: chemical synthesis versus in vivo biosynthesis ... The total synthesis of nisin aims to replicate this precise molecular architecture outside of a biological system. This endeavor is not merely an academic exercise; it opens avenues for creating modified nisin variants with enhanced stability, altered activity profiles, or improved delivery mechanisms. Researchers have explored various synthetic strategies, including fragment condensation and desulfurization approaches, to assemble the complex peptide backbone and form the characteristic lanthionine bridges.

Solid-Phase Peptide Synthesis: A Cornerstone for Nisin Analogues

Solid-phase peptide synthesis (SPPS) has emerged as a workhorse technique for the efficient and controlled assembly of peptides, including nisin and its derivatives. In SPPS, amino acids are sequentially added to a growing peptide chain anchored to an insoluble solid support, typically a resin. This method greatly simplifies purification, as excess reagents and byproducts can be washed away after each coupling stepNisin - Antibacterial Peptide for Microbial Control. The widely used Fmoc/tBu strategy, for instance, employs a base-labile Nα-fluorenylmethyloxycarbonyl (Fmoc) protecting group and acid-labile side-chain protecting groups.

Researchers leverage SPPS to synthesize not only full-length nisin but also key fragments and modified analogues. For instance, studies have focused on creating individual ring structures from nisin or synthesizing analogues where dehydro residues are replacedSolid-Phase Synthesis of C-Terminus Cysteine Peptide Acids. The synthesis of lipopeptide analogues and A-ring analogues of nisin has also been successfully achieved using SPPS techniques. This ability to systematically modify the peptide sequence or introduce non-natural amino acids allows for the fine-tuning of nisin's properties作者：R Dickman·2019·被引用次数：54—We have usedsolid-phase peptide synthesisto prepare individual ring A and B structures from nisin, the related lantibiotic mutacin, and synthetic analogues.. For example, incorporating different amino acids or creating thioamide links has been explored to investigate structure-activity relationships and potentially enhance bioactivity against resistant strains like methicillin-resistant *Staphylococcus aureus* (MRSA)Peptide synthesis.

Expanding the Scope: Nisin Hybrids and Beyond

The synthetic versatility offered by SPPS extends to the creation of hybrid molecules. Researchers have synthesized nisin-peptoid hybrids, combining the antibacterial efficacy of nisin with the properties of peptoids (N-substituted glycine oligomers)Lanthipeptides: chemical synthesis versus in vivo biosynthesis .... These hybrid constructs have demonstrated promising low micromolar activity, comparable to natural nisin, against challenging pathogens. Furthermore, synthetic polyproline peptides have been coupled with nisin fragments to generate novel hybrids, expanding the chemical space for antimicrobial peptide research.Solid-Phase Synthesis of C-Terminus Cysteine Peptide Acids

The total chemical synthesis of other lantibiotics, such as Aureocin A53 and Lacticin Q, using SPPS and native chemical ligation (NCL), highlights the broader impact of these methodologies in the field of peptide chemistry. These advancements not only deepen our fundamental understanding of peptide structure and function but also pave the way for the development of new therapeutic agents.Synthesis of Antibacterial Nisin-Peptoid Hybrids Using ... The ability to precisely control peptide synthesis, whether through solution-phase or solid-phase approaches, is fundamental to exploring the vast potential of these complex and biologically active molecules.