Passage
Solid-phase peptide synthesis is normally carried out on a resin bathed multiple times in dimethylformamide (DMF) -a toxic, polar, aprotic solvent-which poses an environmental problem because a large amount of toxic solvent waste is created. Cyclic carbonates such as propylene carbonate (PC) and ethylene carbonate (EC) are nontoxic, polar, aprotic solvents that could be used as an alternative to DMF.Compounds 1 and 2 are modified L-amino acids. They were coupled to form Compound 3, a dipeptide, which was then deprotected to yield Compound 4 (Figure 1) .
Figure 1 Synthesis of Compound 4To determine the effect that solvent type and temperature have on the synthesis of this peptide, the nontoxic solvents PC and EC as well as the toxic solvent DMF were each used in separate syntheses of Compound 4 at different temperatures. The reaction solvent was also used to rinse the resin. Table 1 shows the results of these syntheses.Table 1 Results from the Synthesis of Compound 4
The successful synthesis of Compound 4 using nontoxic solvents encouraged researchers to pursue the synthesis of a larger, biologically active peptide. Bradykinin, a vasodilator containing nine amino acids (Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg) , was synthesized using the same solid-state peptide synthesis protocol used to synthesize Compound 4. Separate syntheses were done using either DMF or PC, and the purity of bradykinin from each synthesis was analyzed by high-performance liquid chromatography (HPLC) (Figure 2) .In each chromatogram, peak 1 has the same retention time as commercially obtained bradykinin, and the other peaks correspond to impurities. In chromatogram A, the impurity has a similar retention time to the product peak whereas the impurity peaks in chromatogram B have distinct retention times compared to the product peak.
Figure 2 HPLC of synthetic bradykinin: (A) synthesis in DMF; (B) synthesis in PC
Adapted from S. B. Lawrenson et al., "The greening of peptide synthesis." Green Chem. ©2017 The Royal Society of Chemistry.
-What is the byproduct of the formation of Compound 3 described in the passage?

Question

Passage
Solid-phase peptide synthesis is normally carried out on a resin bathed multiple times in dimethylformamide (DMF) -a toxic, polar, aprotic solvent-which poses an environmental problem because a large amount of toxic solvent waste is created. Cyclic carbonates such as propylene carbonate (PC) and ethylene carbonate (EC) are nontoxic, polar, aprotic solvents that could be used as an alternative to DMF.Compounds 1 and 2 are modified L-amino acids. They were coupled to form Compound 3, a dipeptide, which was then deprotected to yield Compound 4 (Figure 1) .

Figure 1 Synthesis of Compound 4To determine the effect that solvent type and temperature have on the synthesis of this peptide, the nontoxic solvents PC and EC as well as the toxic solvent DMF were each used in separate syntheses of Compound 4 at different temperatures. The reaction solvent was also used to rinse the resin. Table 1 shows the results of these syntheses.Table 1 Results from the Synthesis of Compound 4

The successful synthesis of Compound 4 using nontoxic solvents encouraged researchers to pursue the synthesis of a larger, biologically active peptide. Bradykinin, a vasodilator containing nine amino acids (Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg) , was synthesized using the same solid-state peptide synthesis protocol used to synthesize Compound 4. Separate syntheses were done using either DMF or PC, and the purity of bradykinin from each synthesis was analyzed by high-performance liquid chromatography (HPLC) (Figure 2) .In each chromatogram, peak 1 has the same retention time as commercially obtained bradykinin, and the other peaks correspond to impurities. In chromatogram A, the impurity has a similar retention time to the product peak whereas the impurity peaks in chromatogram B have distinct retention times compared to the product peak.

Figure 2 HPLC of synthetic bradykinin: (A) synthesis in DMF; (B) synthesis in PC
Adapted from S. B. Lawrenson et al., "The greening of peptide synthesis." Green Chem. ©2017 The Royal Society of Chemistry.
-What is the byproduct of the formation of Compound 3 described in the passage?

Quizplus · Accepted Answer

11ecba2d_1298_ef86_a3bf_8daa97467963_MD0008_00 Peptides are made up of two or more amino acids linked together through an amide bond, known as a peptide bond. The amino group of one amino acid reacts with the carboxyl group of another amino acid to form a peptide bond through a dehydration reaction. The carboxyl group of one amino acid loses a hydroxyl group (-OH), and the amino group of the other loses a hydrogen atom, releasing H₂O as a byproduct. Compound 3 is described as a dipeptide in the passage and is formed from Compounds 1 and 2 (both modified amino acids). The carboxyl group of Compound 1 and the amino group of Compound 2 undergo a dehydration reaction to form a peptide bond and release H₂O as a byproduct. (Choice B) H₂O is a byproduct, but peptide bond formation is a dehydration reaction rather than a hydrolysis reaction because water is released upon bond formation. Hydrolysis requires the addition of H₂O across a peptide bond, causing peptide bond cleavage. (Choices C and D) The formation of a peptide bond is a coupling reaction, but H₂O is released rather than CO₂. CO₂ is released in a decarboxylation reaction. Educational objective: Peptide bonds are formed through a dehydration reaction, in which the carboxyl group of one amino acid loses a hydroxyl group and the amino group of another amino acid loses a hydrogen atom. H₂O is released as a byproduct in a dehydration reaction.

Passage Solid-Phase Peptide Synthesis Is Normally Carried Out on a Resin