Nuclear power could continue to be a reliable and carbon-free energy source at least from a near-term perspective. In addition to the safety issues, another risk that may threaten the sustainability of this technology is the uranium supply disruption. As opposed to the land-based deposits, the ocean contains 1,000 times more uranium reserves and provides a more abundant resource for uranium. However, due to the very low concentration and presence of many other metal ions as well as the accumulation of microorganisms, the development of uranium extraction technology faces enormous challenges. Here we report a bifunctional polymeric peptide hydrogel that shows not only strong affinity to and selectivity for uranium in seawater but also remarkable resistance against biofouling. Detailed characterizations reveal that the amino acid in this peptide material serves as the binding ligand, and uranyl is exclusively bound to the oxygen atoms. Benefiting from its broad-spectrum antimicrobial activity, the present polymeric adsorbent can inhibit the growth of approximately 99% of marine microorganisms. Measurements in natural seawater show that this peptide material delivers an impressive extraction capacity of 7.12 mg g−1 and can be reused. This work opens a new direction for the design of low-cost and sustainable materials for obtaining nuclear fuel. The oceans contain 1,000 times more uranium than terrestrial resources, which could contribute to the sustainability of nuclear power. Here the authors report a polymeric adsorbent that can capture uranium from seawater selectively with an extraction capacity of 7.12 mg g–1. It is even resistant against biofouling and can be reused.

Selective extraction of uranium from seawater with biofouling-resistant polymeric peptide

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

https://digital.csic.es/bitstream/10261/246390/1/GC-CRV-11-2019-003982.R1_Proof_hi.pdf

Greening Fmoc/tBu solid-phase peptide synthesis

Solid-phase peptide synthesis (SPPS) is generally the method of choice for the chemical synthesis of peptides, allowing routine synthesis of virtually any type of peptide sequence, including complex or cyclic peptide products. Importantly, SPPS can be automated and is scalable, which has led to its widespread adoption in the pharmaceutical industry, and a variety of marketed peptide-based drugs are now manufactured using this approach. However, SPPS-based synthetic strategies suffer from a negative environmental footprint mainly due to extensive solvent use. Moreover, most of the solvents used in peptide chemistry are classified as problematic by environmental agencies around the world and will soon need to be replaced, which in recent years has spurred a movement in academia and industry to make peptide synthesis greener. These efforts have been centred around solvent substitution, recycling and reduction, as well as exploring alternative synthetic methods. In this review, we focus on methods pertaining to solvent substitution and reduction with large-scale industrial production in mind, and further outline emerging technologies for peptide synthesis. Specifically, the technical requirements for large-scale manufacturing of peptide therapeutics are addressed.

/pdf/greening-the-synthesis-of-peptide-therapeutics-an-industrial-2it7wkst5q.pdf

Greening the synthesis of peptide therapeutics: an industrial perspective

Amide bond forming reactions are critical for both polypeptide synthesis and medicinal chemistry. Most current approaches for amidation employ stoichiometric activating agents, but such methods are neither atom economical nor synthetically elegant. Catalytic approaches for amidation are potentially green and more ideal substitutes for current standard methods and thus are the subject of this review. Such methods face significant thermodynamic and kinetic barriers and have, as a result, historically conceded the use of elevated temperatures and dehydrating agents or lacked broad and relevant substrate scopes from the perspective of peptide chemistry. Recent advancements in methods for both direct amidation (the coupling of a carboxylic acid and an amine) and indirect amidation (the coupling of other partners resulting in an amide bond) based on aryl boronic acids, transition metals and organocatalysis for the former and ester amidation and redox‐coupled amidation for the later, address these previous shortcomings and are examined therein.

Recent developments in catalytic amide bond formation

2D green SPPS: green solvents for on-resin removal of acid sensitive protecting groups and lactamization

Aiming at elevating the environmental profile of the solid-phase peptide synthesis (SPPS) methodology by improving the quality of crude peptides that SPPS provides we assessed a series of benzylthiols (BTs) as scavengers for global deprotection/TFA cleavage of exenatide peptide resin accessed by Fmoc SPPS. In these studies we identified 1,4-BDMT as a scavenger that affords the peptide in higher quality than the standard aliphatic thiol reagents, not least in terms of the content of critical peptide impurities in the crude material. Further, 1,4-BDMT exhibited favorable UV detectability as well as stability and solubility in TFA. Finally, based on the MS assessment of the crude exenatide products herein we propose that thiol scavengers in the cleavage of Trp containing peptide resins do not minimize the content of Trp oxidants by means of inhibiting Trp oxidation but rather by forming a peptide–thiol adduct via a mechanism involving an attack of a thiol on an oxindolylalanine (Oia) impurity present in the crude material.

/pdf/1-4-benzenedimethanethiol-1-4-bdmt-as-a-scavenger-for-er6nf9bysh.pdf

1,4-Benzenedimethanethiol (1,4-BDMT) as a scavenger for greener peptide resin cleavages

Sustainable, cost-efficient manufacturing of therapeutic peptides using chemo-enzymatic peptide synthesis (CEPS)

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2D green SPPS: green solvents for on-resin removal of acid sensitive protecting groups and lactamization

1,4-Benzenedimethanethiol (1,4-BDMT) as a scavenger for greener peptide resin cleavages

Sustainable, cost-efficient manufacturing of therapeutic peptides using chemo-enzymatic peptide synthesis (CEPS)