Question

One method for separating polypeptides makes use of their different solubilities. The solubility of large polypeptides in water depends on the relative polarity of their R groups, particularly on the number of ionized groups: the more ionized groups there are, the more soluble the polypeptides are. Which of each pair of polypeptides is more soluble at the indicated \(\mathrm{pH}\) ? a. (Gly) \(_{20}\) or (Glu) \(_{20}\) at pH \(7.0\) b. (Lys- Val) 3 or (Phe-Cys) \(_{3}\) at pH \(7.0\) c. (Ala-Ser-Gly) \(_{5}\) or (Asn-Ser-His) \(_{5}\) at \(\mathrm{pH} 6.0\) d. \((\mathrm{Ala}-\mathrm{Asp}-\mathrm{Phe})_{5}\) or \((\mathrm{Asn}-\mathrm{Ser}-\mathrm{His})_{5}\) at \(\mathrm{pH} 3.0\)

Short answer

(Glu)_{20}, (Lys-Val)_{3}, (Asn-Ser-His)_{5}, and (Ala-Asp-Phe)_{5} are more soluble.

Step-by-step solution

Understand Polypeptide Solubility

The solubility of polypeptides in water is influenced by the number of ionized groups. Peptides with more ionizable groups are generally more soluble. At a given pH, certain amino acids may be charged or uncharged, affecting solubility.

Analyze (Gly)_{20} vs. (Glu)_{20} at pH 7.0

(Gly)_{20} is composed of glycine, which does not have ionizable side chains, while (Glu)_{20} consists of glutamic acid, whose side chains are negatively charged (ionized) at pH 7.0. Thus, (Glu)_{20} has more ionized groups and is more soluble.

Analyze (Lys-Val)_{3} vs. (Phe-Cys)_{3} at pH 7.0

(Lys-Val)_{3} includes lysine, which has a positively charged side chain at pH 7.0, whereas (Phe-Cys)_{3} contains cysteine, which is not ionized and phenylalanine, which is non-polar. (Lys-Val)_{3} is more soluble due to lysine's ionization.

Analyze (Ala-Ser-Gly)_{5} vs. (Asn-Ser-His)_{5} at pH 6.0

Hisidine (His) can be positively charged at pH 6.0, as its pKa is around 6.0, while the other amino acids in both tripeptides are generally not ionized. Therefore, (Asn-Ser-His)_{5} is more soluble due to the ionization of histidine.

Analyze (Ala-Asp-Phe)_{5} vs. (Asn-Ser-His)_{5} at pH 3.0

At pH 3.0, histidine will not be ionized, but aspartic acid in (Ala-Asp-Phe)_{5} might be protonated (uncharged), and phenylalanine is non-polar. (Asn-Ser-His)_{5} doesn't become particularly charged, but generally at lower pH, proteins that could retain some charge or have unchanged solubility predisposed by structure might be considered briefly. In this case, either could potentially have solubility, but logic dictates focusing charge interactions.

Key concepts

Amino Acid Ionization

Ionization of amino acids is a fundamental concept to grasp when understanding the solubility of polypeptides. Each amino acid has a side chain with varying potential for ionization, which largely affects how it interacts with water. Some amino acids have side chains that can either accept or donate protons, thus becoming charged ions. Additionally, the ionization state of particular amino acids is pH-dependent, meaning the pH of the environment is crucial to whether the amino acid side chains are charged or uncharged.

For example, amino acids like glutamic acid and lysine have ionizable side chains. Glutamic acid's side chain tends to lose a proton and becomes negatively charged in a neutral or basic environment. Meanwhile, lysine's side chain can gain a proton and be positively charged at neutral pH. Knowing the ionization potential of the amino acid side chains helps predict their solubility in water because ions typically increase the solubility due to their affinity for water molecules.

Solubility Factors

The solubility of polypeptides is determined by various factors, with the number of ionized groups in the polypeptide being significant. When amino acids with ionizable side chains are present, especially in greater numbers, the polypeptide is generally more soluble. This is because ionized or charged groups enhance interactions with water molecules through hydrogen bonding and electrostatic interactions.

Several factors affect solubility:

• Charge: Ionized groups increase solubility.
• Polarity: Polar side chains interact better with water than non-polar ones.
• Molecular structure: How the polypeptide's structure exposes its charges can also affect solubility.

As these factors interplay, they determine whether a polypeptide will dissolve effectively in an aqueous environment. Amino acids with side chains that can form hydrophilic interactions promote the dissolution in water, whereas hydrophobic side chains tend to lower solubility.

pH and Solubility

The pH of a solution is a critical determinant of polypeptide solubility because it influences the ionization state of amino acid residues. The pH scale measures the acidity or basicity of an environment, affecting how protons interact with molecules like amino acids. Each amino acid has a specific pKa, which is the pH at which half of the population of that amino acid's ionizable group is protonated.

Adjusting the pH can alter the charge states of amino acids within the polypeptide. For instance, at different pH levels, you might find that the ionizable side chains become neutral or charged, directly impacting solubility. For example, at low pH, more amino groups may become protonated, increasing positive charge, while at high pH, more carboxyl groups lose protons, increasing negative charge.

Understanding how pH alters the total charge of polypeptides is essential for predicting their solubility. It also allows for strategic manipulation of pH conditions to optimize solubility for specific analytical or industrial applications.