Rapid solid-phase peptide synthesis using thermal and controlled microwave irradiation

Bacsa, Bernadett; Desai, Bimbisar; Dibó, Gábor; Kappe, C. Oliver

doi:10.1002/psc.771

Cited by 74 publications

(57 citation statements)

References 18 publications

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“…Fibrinopeptide-B (EGVNDNEEGFFSAR) and its analogue, i.e., REGVND-NEEGFFSA, and REGVNDNEEGFFSAR, were synthesized in-house using a Personal Synthesizer (Peti-Syzer model PSS-510; HiPep Laboratories, Kyoto, Japan) and were used without further purification. Standard Fmoc synthesis procedures were employed [22][23][24]. All reagents used for peptide synthesis were obtained from Sigma and Aldrich (St. Louis, MO, USA), LC Science (Houston, TX, USA) and Advanced ChemTech (Creo Salus Inc., Louisville, KY, USA).…”

Section: Methodsmentioning

confidence: 99%

Natural structural motifs that suppress peptide ion fragmentation after electron capture

Chan

2010

J. Am. Soc. Mass Spectrom.

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Series of doubly and triply protonated diarginated peptide molecules with different number of glutamic acid (E) and asparagine (N) residues were analyzed under ECD conditions. ECD spectra of doubly-protonated peptides show a strong dependence on the number of E and N residues. Both the backbone cleavages and hydrogen radical (H • ) loss from the charge-reduced precursor ions ([Mϩ2H] ϩ• ) were suppressed as the number of E and N residues increases. A strong inhibition of the backbone cleavages and H • loss from [Mϩ2H] ϩ• was found for peptides with 6E residues (or 4E ϩ 2N residues). The results obtained using these model peptides were re-confirmed by analyzing N-arginated Fibrinopeptide-B (i.e., REGVNDNEEGFFSAR). In contrast to the N-arginated peptide, ECD of the doubly-protonated Fibrinopeptide-B and its analogues show extensive backbone cleavages leading to series of c-and z-ions (ϳ80% sequence coverage). Based on these results, it is believed that peptide ions with all surplus protons sequestered in arginine-residues would show enhanced stability under ECD conditions as the number of acid-residue increases. The suppression of backbone cleavages and H • loss from [Mϩ2H] ϩ• are presumably attributed to the low reactivity of the charge-reduced precursor ions. One of the possible hypothesis is that diarginated E-rich peptides may contain hydrogen bonds between carbonyl oxygen of E side chains and backbone amide hydrogen. These hydrogen bonds would provide extra stabilization for [Mϩ2H] -4]. ECD also plays a useful role in characterization and localization of post-translational modifications (PTMs) as it preserves labile PTMs in protein [5][6][7] while cleaving the protein backbone to give series of specific fragment ions. This is in contrast with that of conventional slow-heating ion dissociation methods [8,9], such as collision induced dissociation (CID) [10 -12] and infrared multiproton dissociation (IRMPD) [13]. ECD involves the reaction between multiply-charged ions and low-energy electrons. Besides the formation of the charge-reduced precursor ions, [M ϩ nH] (n-1)ϩ• , the recombination energy released might provide enough energy to cause backbone N-C ␣ cleavages producing series of c or z • ions and to a lesser extent series of a • or y ions. Other ECD events include the elimination of (1) a H • to form [M ϩ (n-1)H] (n-1)ϩ , and (2) amino acid side chains from z • ions and/or [M ϩ nH] (n-1)ϩ• . Cleavages in ECD are nonspecific [14], and the relative propensities for dissociation of various amino acid residues were found to fall in a narrow range. Because of the ring-type structure, only fragment ions resulting from the backbone cleavages at the N-terminal side of proline (P) were suppressed [15].The importance of radical in charge-reduced precursor ion in ECD was investigated by synthetically incorporating single and multiple radical trap, spin trap, and charge tag moieties in model peptides. In radical trap experiments, Belyayev et al. [16] attached coumarin labels onto the N-terminal amino group (or/an...

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Section: Methodsmentioning

confidence: 99%

Natural structural motifs that suppress peptide ion fragmentation after electron capture

Chan

2010

J. Am. Soc. Mass Spectrom.

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“…Microwave irradiation may lead to de-aggregation via dipole alignment, allowing increased accessibility of reagents and, hence, more efficient de-protection, coupling, and washing [114].…”

Section: Microwave-assisted Peptide Synthesismentioning

confidence: 99%

Evolution of microwave irradiation and its application in green chemistry and biosciences

2011

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Microwave-assisted organic reactions have been applied as an effective technique in organic synthesis. Microwave irradiation often leads to shorter reaction times, increased yields, easier workup, matches with green chemistry protocols, and can enhance the region and stereo selectivity of reactions. In fact, the high usefulness of microwave-assisted synthesis encouraged us to increase the efficiency of several organic transformations and synthesis. High-speed microwave-assisted chemistry has attracted a considerable amount of attention in recent years and has been applied successfully in various fields of synthetic organic chemistry, proteins, peptides, drug discovery, and green chemistry. The various roles of microwaveassisted organic chemistry in green and sustainable chemistry are discussed, beginning with the strategies, technologies, and methods that were employed routinely at the time of the first reports of microwave applications. Microwave processing has several advantages over conventional sintering/heating, such as the reduction in cycle time, energy efficiency, eco-friendliness, and providing finer microstructures, leading to improved mechanical properties. Herein, we also describe the evolution of the microwave and some early applications of microwave assistance in the biomolecular sciences and treatment of solid malignant tumors.

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“…Moreover, it is generally believed that undesirable side reactions would also be accelerated by microwave heating and that some coupling reagents are heat sensitive. Nevertheless, SPPS with microwave was successfully applied in the synthesis of peptides [56][57][58].…”

Section: Microwave Synthesismentioning

confidence: 99%

Purity profiling of Peptide Drugs

Verbeken¹

2012

JBABM

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The quality of a peptide drug mainly depends on its impurity profile, with the emphasis on the related impurities. These impurities may be biomedically active, alter the desired efficacy or induce unwanted toxicity, an aspect which is termed the "functional quality" of the peptide drug. Therefore, regulatory authorities have set up guidances or have legally established specification limits to assure a consistent purity of these peptide drugs. For the active pharmaceutical ingredients (APIs), the pharmacopoeial monographs are legally binding. Additional information can be found in regional and international guidelines. For the finished pharmaceutical drug products (FDPs) containing peptide active ingredients, only general guidelines are available. The construction of a complete related-impurity profile is very challenging due to the wide availability of different protecting groups, coupling agents and additives that may be used during peptide synthesis. In addition, chemical degradation, occurring during synthesis, formulation or at storage, may occur as well, including not only so-called pure chemical degradation but interaction with excipients as well. This review provides an update of the regulatory and scientific rationales behind the related impurities in peptide drugs.

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Rapid solid-phase peptide synthesis using thermal and controlled microwave irradiation

Cited by 74 publications

References 18 publications

Natural structural motifs that suppress peptide ion fragmentation after electron capture

Natural structural motifs that suppress peptide ion fragmentation after electron capture

Evolution of microwave irradiation and its application in green chemistry and biosciences

Purity profiling of Peptide Drugs

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