c-peptide-in-type-1-and-type-2-diabetes The synthesis of prochlorosins, a class of cyclic peptides produced by marine cyanobacteria like *Prochlorococcus*, can be achieved through various methods, with solid-phase peptide synthesis (SPPS) emerging as a key technique. SPPS offers a versatile and efficient route to construct these complex molecules, allowing for the systematic study of their structure-activity relationships and the development of novel analogs. This approach involves assembling the peptide chain on a solid support, typically a resin, which simplifies purification and enables the synthesis of challenging sequences.
Prochlorosins are characterized by their unique post-translational modifications, including dehydrations and the formation of thioether rings, which are crucial for their biological activity. Understanding these modifications is central to their synthetic efforts. While natural biosynthesis involves intricate enzymatic machinery, chemical synthesis, particularly SPPS, provides a controlled environment to mimic or explore these processes.Structural Characterization of Four Prochlorosins - PMC - NIH The ability to incorporate labeled amino acids, such as deuterium-labeled serine and threonine, during SPPS is also vital for tracking metabolic pathways and understanding the biosynthesis of these peptides.
Solid-phase peptide synthesis (SPPS) has become an indispensable tool in the study and production of peptides, including complex natural products like prochlorosins.作者：JH Urban·2017·被引用次数：124—Here we report the engineering of lanthipeptides, a subclass of RiPPs characterized by multiple thioether cycles that are enzymatically introduced in a regio- ... The fundamental principle of SPPS involves sequentially adding amino acids to a growing peptide chain anchored to an insoluble polymer resin作者：P Arias-Orozco·2023·被引用次数：18—To release the SyncA corepeptide, we added an ASPR cleavage site behind the −1 G position, which is conserved inprochlorosinand synechococsin .... This method offers several advantages over traditional solution-phase synthesis, especially for longer or more complex peptides:
* Simplified Purification: Excess reagents and byproducts are easily washed away with the resin, eliminating the need for intermediate purification steps after each amino acid coupling.
* Automation Potential: SPPS is amenable to automation, allowing for the rapid synthesis of multiple peptide sequences and libraries.
* High Yields: The excess of reagents used in SPPS can drive reactions to completion, often resulting in higher yields of the desired peptideConvergent solid phase peptide synthesisvi : synthesis by the fmoc procedure with a modified protocol of two protected segments, sequence 5-17 and 18-31 of ....
* Access to Difficult Sequences: SPPS strategies can be adapted to overcome challenges associated with synthesizing peptides containing unusual amino acids or complex structural motifs, such as the cyclic structures found in prochlorosins.
The Fmoc/tBu (9-fluorenylmethoxycarbonyl/tert-butyl) strategy is a widely adopted method in SPPS for prochlorosin synthesis.2023年6月5日—SPPS is a method used to create peptidesby assembling amino acids in a stepwise fashion on a solid support, such as a resin. This strategy utilizes orthogonal protecting groups, where the N-terminal Fmoc group is removed under mild basic conditions, and side-chain protecting groups (often tert-butyl based) are stable to these conditions but are cleaved simultaneously with the peptide from the resin under acidic conditions. This allows for the controlled elongation of the peptide chain作者：JH Urban·2017·被引用次数：124—Here we report the engineering of lanthipeptides, a subclass of RiPPs characterized by multiple thioether cycles that are enzymatically introduced in a regio- ....
Synthesizing prochlorosins via SPPS requires careful consideration of several factors to ensure successful assembly and the formation of the characteristic cyclic peptide structure and thioether linkages.Cyanobacteria and Eukaryotic Microalgae as Emerging ...
The selection and management of protecting groups are paramount in SPPSConvergent solid phase peptide synthesisvi : synthesis by the fmoc procedure with a modified protocol of two protected segments, sequence 5-17 and 18-31 of .... For prochlorosins, specific amino acid side chains may require protection to prevent unwanted side reactions during peptide elongation. For instance, residues that will eventually form thioether bonds often require specific precursors or modified amino acids that can be elaborated post-assembly作者：S Mukherjee·2015·被引用次数：1—Solid phase peptide synthesis (SPPS) was used to generate the substrates to study ProcM, and is also a flexibile tool to access non-native .... The C-terminal linkage to the resin also plays a role, with different resins and linkers being chosen based on the desired C-terminal functionality of the final peptide.作者：D Liu·2021·被引用次数：24—Solid-phase peptide synthesis: from standard procedures to the synthesis of difficult sequences. Nat. Protoc. 2007; 2:3247-3256. Crossref.
A defining feature of prochlorosins and other lantibiotics is the presence of thioether rings, typically formed through the cyclization of cysteine residues with dehydroalanine or dehydrobutyrine residuesEmploying the promiscuity of lantibiotic biosynthetic .... In SPPS, this can be achieved through various approaches:
* Post-assembly Modification: After the linear peptide is synthesized and cleaved from the resin, cyclization reactions can be performed in solution. This often involves controlled oxidation or other chemical reactions to form the thioether bonds.
* On-resin Cyclization: In some cases, cyclization can be initiated while the peptide is still attached to the solid support, which can facilitate certain types of ring closures.
The regioselectivity of these cyclizations is critical, as the specific positions of the thioether rings determine the peptide's three-dimensional structure and biological activity.Investigating the Specificity of the Dehydration and ... Research into the enzymatic machinery responsible for these modifications in nature has provided insights that guide synthetic strategies.作者：JM Palomo·2014·被引用次数：476—This review article highlights the strategies to successfully perform an efficientsolid-phase synthesisof complexpeptidesincluding ...
To study the biosynthesis and mechanism of action of prochlorosins, synthetic peptides incorporating deuterium-labeled amino acids (e.g.A lanthipeptide library used to identify a protein ... - ePrints Soton, deuterium-labeled serine and threonine) are often synthesized作者：K Jeanne Dit Fouque·2021·被引用次数：11—Prochlorosin2.8. (Pcn2.8) is a class II lanthipeptide that exhibits a non-overlapping thioether ring pattern, for which no biological activity has been .... SPPS provides a straightforward way to incorporate these labeled building blocks at specific positions within the peptide sequence.2023年6月5日—SPPS is a method used to create peptidesby assembling amino acids in a stepwise fashion on a solid support, such as a resin. This allows researchers to trace the peptide's fate in biological systems or to monitor specific enzymatic reactions involved in its maturation.
Despite the advancements in SPPS, the synthesis of complex cyclic peptides like prochlorosins still presents challenges. These include achieving efficient cyclization, controlling regioselectivity, and synthesizing peptides with high purity and yield, especially for larger or more intricate structures.
Future research in prochlorosin synthesis will likely focus on developing more efficient and selective methods for thioether formation, exploring novel solid supports and linker chemistries, and integrating SPPS with other synthetic techniques, such as native chemical ligation, to access even more complex peptide architectures作者：S Mukherjee·2014·被引用次数：82—(25-27) In this study, we experimentally probed a potential role of non-enzymatic cyclization inprochlorosinmaturation. The substrate-tolerant .... The continued development of SPPS methodologies will undoubtedly accelerate our understanding of prochlorosins and potentially lead to the discovery of new therapeutic agents or biochemical tools作者：SC Bobeica·2018·被引用次数：19—Appropriately protected commercially available [2,3,3-D3]-Ser or [2,3-D2]-Thr is used in standard Fmoc-basedsolid-phase peptide synthesis(SPPS) and manually ....
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