Question

Which of the following peptides have a net positive charge at pH 7? (a) Gly- Ser-Lys, (b) Pro-Leu-Ile, (c) PheTyr-Asp.

Short answer

The peptide with a net positive charge at pH 7 is (a) Gly-Ser-Lys. This is because its net charge at this pH is +1, as calculated by summing the charges of its individual amino acids, N-terminus, and C-terminus.

Step-by-step solution

At pH 7, acidic amino acids Asp and Glu will be negatively charged (-1), basic amino acids Arg, Lys, and His will be positively charged (+1), and the remaining amino acids will have no charge. Here is the list of amino acids present in each peptide with their corresponding charges at pH 7: (a) Gly (0), Ser (0), Lys (+1) (b) Pro (0), Leu (0), Ile (0) (c) Phe (0), Tyr (0), Asp (-1) #Step 2: Calculate charges contributed by N-terminus and C-terminus#

N-terminal pKa values are typically around 9, while C-terminal pKa values are around 2. At pH 7: - The N-terminus will contribute a positive charge because its pKa > 7 - The C-terminus will contribute a negative charge because its pKa < 7 #Step 3: Add up the charges to find the net charge of each peptide at pH 7#

Now, let's add up the charges from the individual amino acids, N-terminus, and C-terminus to compute the net charge of each peptide: (a) Gly-Ser-Lys: 0 + 0 + 1 (+1 at N-terminus) + (-1 at C-terminus) = +1 (b) Pro-Leu-Ile: 0 + 0 + 0 (+1 at N-terminus) + (-1 at C-terminus) = 0 (c) Phe-Tyr-Asp: 0 + 0 - 1 (+1 at N-terminus) + (-1 at C-terminus) = -1 #Step 4: Identify which peptides have a net positive charge#

Comparing the net charges of the given peptides, we see that: (a) Gly-Ser-Lys has a net positive charge at pH 7 (b) Pro-Leu-Ile has a neutral charge (c) Phe-Tyr-Asp has a net negative charge Thus, the peptide with a net positive charge at pH 7 is (a) Gly-Ser-Lys.

Key concepts

Peptide Net Charge

Understanding the net charge of a peptide is crucial for studying its behavior in biological systems, such as how it interacts with other molecules and membranes. At a given pH, the net charge of a peptide is determined by the sum of the charges of its constituent amino acids, including any charges contributed by the N-terminus and C-terminus.

For example, at pH 7, neutral pH, most amino acids have no charge, with the exception of the acidic amino acids (like Asp and Glu), which are negatively charged, and basic amino acids (such as Arg, Lys, and His), which are positively charged. The net charge is the algebraic sum of these individual amino acid charges along with the terminal charges.

A peptide with an equal number of positively and negatively charged amino acids will have a net charge of zero. However, if there is an imbalance—more positive than negative or vice versa—the peptide will have a corresponding net positive or negative charge, respectively. It's essential, for accuracy, to take into account the influence of the pH on the ionization of the amino acid side chains and terminals to get a reliable calculation of the peptide net charge.

N-terminus and C-terminus Charges

The N-terminus (amino end) and C-terminus (carboxyl end) of a peptide can contribute to its overall net charge due to their ionizable nature. At physiological pH, which is approximately 7, the N-terminus tends to be protonated and carries a positive charge because its pKa is above 7. Conversely, the C-terminus usually has a negative charge since its pKa is below 7.

This means that, regardless of the side chain charges, peptides will inherently start with a baseline charge of zero, with the N-terminus contributing a +1 charge and the C-terminus contributing a -1 charge. To evaluate the overall charge of a peptide, we always have to include these contributions in the calculation, along with the charges of the amino acids that make up the peptide chain. This is critical to anticipate the peptide's behavior, including its solubility and interaction potential with other molecules in solution at a specific pH.

Acidic and Basic Amino Acids

Amino acids are building blocks of proteins and each has a distinctive side chain that can be neutral, acidic, or basic. At pH 7, acidic amino acids, such as aspartic acid (Asp) and glutamic acid (Glu), will lose a proton and carry a negative charge. Basic amino acids, including arginine (Arg), lysine (Lys), and histidine (His), will accept a proton and bear a positive charge.

The charge of an amino acid is not only important by itself but also has broader implications on the behavior of the entire peptide it constitutes. For example, a peptide chain with a greater number of acidic amino acids will tend to have a net negative charge, while one with more basic amino acids will more likely display a net positive charge.

Charge Relationships

Understanding the charge relationships within a peptide allows us to predict not only solubility and stability but also how the peptide might interact with surrounding environments or participate in biochemical processes. It's a foundational principle in biochemistry with applications ranging from drug design to understanding cellular mechanisms.