Green Peptide Synthesis Using Environmentally Sustainable Deep Eutectic Solvents
Disciplines
Analytical Chemistry | Medicinal-Pharmaceutical Chemistry
Abstract (300 words maximum)
In last decades, peptide therapeutics received great attention over small-molecule medications, as they are highly selective, well-tolerated, and have less adverse effects. There are ~70 therapeutic peptides on the market, ~200 in clinical trials, and ~600 in the pre-clinical development stage. Peptides can be synthesized by liquid phase as well as solid phase. Solid-phase peptide synthesis (SPPS) offer many advantages. SPPS is faster due to few steps, easy to separate excess reagents and by-products, and very cost-effective compared to the liquid-phase peptide synthesis. The whole SPPS processes significantly rely on the usage of sizable amounts of solvent. The solvent plays a pivotal role on swelling of resin, dissolving deprotection reagents, Fmoc amino acids, and coupling reagents and removing excess reagent and by-products through extensive and repetitive washing. The most common solvents used for solid phase synthesis are N,N-Dimethylformamide (DMF) and N-Methyl-2-pyrrolidone (NMP) which have reproductive toxicity. As hazard solvents represent 80−90% of the total waste in SPPS, hence, using green solvents or alternative ways to diminish or recycle solvents are of great interest.
Deep eutectic solvents (DESs) have emerged as green solvents with superior properties over conventional solvents. DESs are more synthetically accessible with negligible vapor pressure, typically nontoxic, biodegradable, economical, and suitable for biological applications. In this study, we have synthesized a small tripeptide containing glycine-alanine-Serine (GAS) manually using DMF as control solvent and choline chloride (ChCl)-glycerol (Glyol) DES as an emerging alternative. The synthesis was performed in a syringe containing frit clamped above an Erlenmeyer flask used to capture access reagent and solvents. The mass spectra of the GAS peptides synthesized in DMF and ChCl-Glyol are determined by Thermo Scientific LTQ-XL mass spectrometer. Both cases, the peak obtained at m/z 233 confirmed the theoretical mass of the peptide. Formation of the sodium adduct is noticed in both cases.
Academic department under which the project should be listed
CSM - Chemistry and Biochemistry
Primary Investigator (PI) Name
Mohammad A. Halim
Green Peptide Synthesis Using Environmentally Sustainable Deep Eutectic Solvents
In last decades, peptide therapeutics received great attention over small-molecule medications, as they are highly selective, well-tolerated, and have less adverse effects. There are ~70 therapeutic peptides on the market, ~200 in clinical trials, and ~600 in the pre-clinical development stage. Peptides can be synthesized by liquid phase as well as solid phase. Solid-phase peptide synthesis (SPPS) offer many advantages. SPPS is faster due to few steps, easy to separate excess reagents and by-products, and very cost-effective compared to the liquid-phase peptide synthesis. The whole SPPS processes significantly rely on the usage of sizable amounts of solvent. The solvent plays a pivotal role on swelling of resin, dissolving deprotection reagents, Fmoc amino acids, and coupling reagents and removing excess reagent and by-products through extensive and repetitive washing. The most common solvents used for solid phase synthesis are N,N-Dimethylformamide (DMF) and N-Methyl-2-pyrrolidone (NMP) which have reproductive toxicity. As hazard solvents represent 80−90% of the total waste in SPPS, hence, using green solvents or alternative ways to diminish or recycle solvents are of great interest.
Deep eutectic solvents (DESs) have emerged as green solvents with superior properties over conventional solvents. DESs are more synthetically accessible with negligible vapor pressure, typically nontoxic, biodegradable, economical, and suitable for biological applications. In this study, we have synthesized a small tripeptide containing glycine-alanine-Serine (GAS) manually using DMF as control solvent and choline chloride (ChCl)-glycerol (Glyol) DES as an emerging alternative. The synthesis was performed in a syringe containing frit clamped above an Erlenmeyer flask used to capture access reagent and solvents. The mass spectra of the GAS peptides synthesized in DMF and ChCl-Glyol are determined by Thermo Scientific LTQ-XL mass spectrometer. Both cases, the peak obtained at m/z 233 confirmed the theoretical mass of the peptide. Formation of the sodium adduct is noticed in both cases.