solid-phase-peptide-synthesis-of-gallidermin-analogues The solid-phase peptide synthesis of nisin is a specialized area of peptide chemistry focused on constructing this complex lantibiotic. Nisin, a natural antimicrobial peptide, is characterized by its unusual amino acids, such as lanthionines and dehydroalanines, which present significant challenges for traditional synthesis methods. Solid-phase peptide synthesis (SPPS) has emerged as a key technology for creating nisin and its analogues, enabling researchers to investigate its structure-activity relationships and develop modified versions with improved properties.作者：R Rink·2007·被引用次数：202—NisinA is a pentacyclic antibioticpeptideproduced by various Lactococcus lactis strains.Nisindisplays four different activities: (i) it autoinduces its ...
Nisin is a pentacyclic peptide with a molecular weight of approximately 3.4 kDa.Lipidated variants of the antimicrobial peptide nisin ... Its unique structure includes multiple thioether bridges formed from lanthionine residues and unsaturated amino acids like dehydroalanine (Dha) and dehydrobutyrine (Dhb). These non-standard amino acids are crucial for nisin's antimicrobial activity but are difficult to incorporate directly using standard peptide synthesis protocols. The presence of these modified residues, along with the peptide's complex ring structures, necessitates advanced synthetic strategiesNisin Variants Generated by Protein Engineering and Their ....
Solid-phase peptide synthesis is a powerful technique for constructing peptides by sequentially adding amino acids to a growing chain anchored to an insoluble solid support. This method simplifies purification by allowing excess reagents to be washed away after each coupling step. For nisin, SPPS offers a flexible platform for:
* Synthesizing Nisin Analogues: Researchers frequently use SPPS to create modified versions of nisin.A Chemical Biology Approach to Understanding Molecular ... This involves altering specific amino acids, such as replacing Dha residues or introducing non-canonical amino acids (ncAAs), to study their impact on antimicrobial activity, stability, or target bindingAn introductory guide tosolid phase peptide synthesis. Resins, amino acid derivatives, coupling reagents, common problems and their solutions, peptide .... For example, analogues of the N-terminus or specific ring structures of nisin have been synthesized to probe structure-function relationships.
* Incorporating Non-Standard Amino Acids: The direct incorporation of residues like Dha into a peptide chain during SPPS can be challenging due to their reactivityEngineering of Nisin as a Means for Improvement of Its .... Specialized coupling reagents and strategies are employed to overcome these difficulties. Microwave-enhanced SPPS has also been utilized to accelerate reaction times and improve efficiency in the synthesis of complex peptides like lantibiotics.
* Building Complex Ring Structures: The synthesis of lanthionine bridges, which are characteristic of nisin and other lantibiotics, requires careful planning within the SPPS framework. Methodologies have been developed to construct these overlapping lanthionine bridges on the solid support, enabling the synthesis of specific ring fragments or complete peptide structures.
Despite its advantages, the solid-phase synthesis of nisin is not without its hurdles. The complex post-translational modifications that occur in nature are difficult to replicate chemicallySemi-synthesis of nisin-based peptide antibiotics - DSpace. Key challenges include:
* Dehydroamino Acid Synthesis: The formation and stability of dehydroalanine (Dha) and dehydrobutyrine (Dhb) residues during SPPS require specific chemical conditions to prevent side reactions or racemization作者：R Dickman·2019·被引用次数：26—We have usedsolid-phase peptide synthesisto prepare two novel analogues ofnisin(1–12) in which the dehydro residues have been replaced..
* Lanthionine Bridge Formation: Creating the thioether linkages that form the characteristic rings of nisin demands precise control over reaction conditions and reagent selection.作者：B Mothia·2011·被引用次数：50—A methodology for thesolid-phase synthesisof the overlapping lanthionine bridges found in many lantibiotics has been developed.
* Yield and Purity: Synthesizing a peptide as complex as nisin on a solid support can result in lower yields and require extensive purification to obtain a pure product, especially when creating analogues with multiple modifications.作者：JC Slootweg·2013—building block insolid phase peptide synthesis. The incorporation of this lipophilic amino acid in an antimicrobial peptide increase the affinity of this ...
Innovations in SPPS, such as the development of new coupling reagents, resins, and automated synthesis platforms, continue to improve the feasibility and efficiency of synthesizing nisin and related lantibiotics作者：R Dickman·2019·被引用次数：26—We have usedsolid-phase peptide synthesisto prepare two novel analogues ofnisin(1-12) in which the dehydro residues have been replaced.. These advancements are crucial for producing sufficient quantities for biological studies and potential therapeutic applications.
The ability to synthesize nisin and its analogues through solid-phase peptide synthesis opens doors for various applicationsHigh-purityNisinantibacterialpeptidefor effective microbial inhibition ... Linkers forSolid Phase Synthesis· Amino Acids 2-Chlorotrityl Resin · Other .... These include:
* Antimicrobial Agents: Modified nisin peptides could offer enhanced potency, broader spectrum activity, or improved stability compared to the native peptide, making them valuable as food preservatives or therapeutic agents against resistant bacterial strains.Guide to Solid Phase Peptide Synthesis - AAPPTEC
* Research Tools: Synthetic nisin fragments and analogues serve as critical tools for understanding the molecular mechanisms of nisin's action, such as its interaction with target molecules like Lipid II, which is essential for bacterial cell wall biosynthesis.
* Drug Discovery: The structural insights gained from synthesizing nisin analogues can guide the design of novel peptide-based drugs with improved pharmacokinetic properties and targeted activityNisin Variants Generated by Protein Engineering and Their ....
In conclusion, solid-phase peptide synthesis of nisin represents a sophisticated chemical endeavor that allows for the detailed study and potential engineering of this important lantibiotic peptide. Ongoing research in synthetic methodologies promises to further enhance our ability to produce and utilize nisin and its derivatives for diverse scientific and practical purposes.
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