Advances in solid-phase peptide synthesis in aqueous media (ASPPS)

Abstract

Peptides are gaining ground in the pharmaceutical arena, with a total of 22 approvals over the last six years. These molecules are also present in antibody-drug conjugate constructs as linkers...

Elevating 1-tert-Butyl-3-ethylcarbodiimide (TBEC) as a Reagent for Sustainable Peptide Synthesis: Quality Assessment and Minimizing Racemization, Precipitation, and Radical-Induced Side Reactions by TBEC/Oxyma Couplings in an Environmentally Sensible Solvent

“…The reliance on DIC/Oxyma has been particularly pronounced in SPPS in greener solvents and investigated extensively in recent years due to health hazards associated with the standard SPPS solvent DMF . In fact, SPPS in greener solvents has relied on DIC/Oxyma practically exclusively, , with only a few coupling protocols not relying on aqueous SPPS, explosive , and allergenic reagents , being reported . Nevertheless, as outlined above, DIC/Oxyma has been confronted by the issue of H-CN formation (Figure c.i), whereas upon using DIC itself, one has to contend with the varying contents of S-containing impurities, which influence the occurrence of radical-induced side reactions (Figure b.i,ii).…”

Unveiling the Configurational Landscape of Carbamate: Paving the Way for Designing Functional Sequence-Defined Polymers

“…1,2 Therefore, significant efforts have been devoted to understand how the structures are controlled in nature and to achieve de novo design of new functional materials through the primary sequence control. 3,4 With the development of sequence-defined peptide synthesis methods, [5][6][7][8][9] the field of peptide-and protein-based functional nanomaterials has flourished to obtain sophisticated structures and fine-tuning functions. 1,[10][11][12] Although polypeptides are a promising class of materials, several challenges remain.…”

Greener Cleavage of Protected Peptide Fragments from Sieber Amide Resin

“…[ 24 , 32 , 38 ] Significant advances were achieved in the development of aqueous SPPS (ASPPS) as well. [39] …”

“…[24,32,38] Significant advances were achieved in the development of aqueous SPPS (ASPPS) as well. [39] Protected peptide fragments are the essential precursors for key subsequent reactions such as cyclization [40] and fragment condensation. [41,42] They can also be utilised to circumvent significant side reactions by introducing peptide fragments rather than the amino acid on its own.…”

“…Various green alternatives have been introduced to the SPPS process, [10,17] aimed at the swelling of the resin, [15,18–27] 9‐fluorenylmethoxycarbonyl (Fmoc) removal, [12,15,18,20–22,24,27–31] the incorporation of the first amino acid onto the resin, [32,33] amide bond formation, [12,14,15,20–25,27,30,34–37] and precipitation [24,32,38] . Significant advances were achieved in the development of aqueous SPPS (ASPPS) as well [39] …”