Sustainability in peptide chemistry: current synthesis and purification technologies and future challenges

Abstract

Developing greener synthetic processes is an inescapable necessity to transform the industrial landscape, mainly in the pharmaceutical sector, into a long-term, sustainable reality. In this context, the renaissance of peptides...

Marine Cyclic Peptides: Antimicrobial Activity and Synthetic Strategies

“…Required tetrapeptide and tripeptide units were prepared by coupling of Boc-protected dipeptides. Cyclization of the linear peptide unit was performed using the pentafluorophenyl ester method [370], which can be easily adapted to automated peptide synthesis systems [294,371]. As a final remark, it is important to highlight that, nowadays, green chemistry is an important concern and challenge in the synthesis of peptides, considering the urgency of protecting the environment from pollution, as well as ensuring that clean water and energy are available for future generations [372].…”

“…In this sense, efforts to improve the environmental profile of the whole SPPS process and to obtain greener downstream purification processes are mandatory to ensure prioritizing of the quality and the purity of the crude peptides. Regarding cleavage steps, TFA As a final remark, it is important to highlight that, nowadays, green chemistry is an important concern and challenge in the synthesis of peptides, considering the urgency of protecting the environment from pollution, as well as ensuring that clean water and energy are available for future generations [371]. A high environmental impact can be observed due to the huge volume of solvents required for the peptide synthesis protocol by SPPS (such as Fmoc/tBu) protection strategy [372], high amounts of reagents are also introduced to push the reaction to completion and minimize the formation of impurities [371].…”

“…Regarding cleavage steps, TFA As a final remark, it is important to highlight that, nowadays, green chemistry is an important concern and challenge in the synthesis of peptides, considering the urgency of protecting the environment from pollution, as well as ensuring that clean water and energy are available for future generations [371]. A high environmental impact can be observed due to the huge volume of solvents required for the peptide synthesis protocol by SPPS (such as Fmoc/tBu) protection strategy [372], high amounts of reagents are also introduced to push the reaction to completion and minimize the formation of impurities [371]. In this sense, efforts to improve the environmental profile of the whole SPPS process and to obtain greener downstream purification processes are mandatory to ensure prioritizing of the quality and the purity of the crude peptides.…”

In situ Fmoc removal – a sustainable solid-phase peptide synthesis approach

“…5 In the context of green chemistry, SPPS has large "green brushstrokes". In this regard, this strategy has the following characteristics: [6][7][8] (i) all reactions are carried out in the same reactor, with no mass transfer between reactors, and no major cleaning procedures; (ii) intermediates are not isolated, thereby lowering solvent consumption; (iii) excellent yields are obtained, which facilitates purification and reduces the use of solvents; (iv) high boiling point solvents are used; (v) solvents can be recycled and the resin can be reused [when a chlorotrityl chloride (CTC) resin is used]; (vi) excess reactants and soluble side products are removed by simple filtration and washing with the corresponding solvents; and, finally, (vii) high efficiency and reduced labor hours are achieved.…”

Application of Af4-Multidetection to Liraglutide in Its Formulation: Preserving and Representing Native Aggregation

“…Peptide candidates can be produced either with chemical or recombinant strategies (upstream process), according to the length of the sequence and from the presence of non-proteinogenic amino acids in the primary structure [ 7 , 8 ]. In both cases, the crude peptides obtained require a purification step (downstream process) to achieve the quality target requested by the national regulatory authorities, using ion exchange and size exclusion chromatography, precipitation, and extraction, even though the reference technique remains ion pair reversed-phase liquid chromatography [ 9 , 10 ]. Once the peptide Active Pharmaceutical Ingredient (API) is produced and purified, and usually lyophilized, it undergoes formulation to reach its Finished Dosage Form (FDF).…”