Question

Propose a structure for an octapeptide that shows the composition Asp, Gly \(_{2}\), Leu, Phe, Pro \(_{2}\), Val on amino acid analysis. Edman analysis shows a glycine N-terminal group, and leucine is the C-terminal group. Acidic hydrolysis gives the following fragments: Val-Pro-Leu, Gly, Gly-Asp-Phe-Pro, Phe-Pro-Val

Short answer

Gly-Gly-Asp-Phe-Pro-Val-Pro-Leu.

Step-by-step solution

List the Given Components

The problem gives us the octapeptide composition as Asp, Gly (2 units), Leu, Phe, Pro (2 units), Val. Edman degradation analysis provides the starting and ending groups: Gly is at the N-terminal and Leu is at the C-terminal. Also, we know the sequence breaks into smaller fragments upon acidic hydrolysis.

Analyze Fragmentation Data

The fragments given are Val-Pro-Leu, Gly, Gly-Asp-Phe-Pro, and Phe-Pro-Val. These fragments must be pieces of the complete octapeptide, and they contain clues about how the amino acids are connected.

Use Known Terminals to Connect Fragments

Since Gly is the N-terminal, and Leu is the C-terminal, look for where these fragments logically connect: the fragment Val-Pro-Leu seems to represent a clear end with Leu as its last amino acid. Gly can only connect as the first in a fragment, like Gly-Asp-Phe-Pro or it can stand alone.

Identify Overlaps in Fragments

Consider overlaps such as Gly in Gly-Asp-Phe-Pro, and the standalone Gly, ensuring that these Glycine units fit the sequence. The Phe-Pro-Val and Gly-Asp-Phe-Pro fragments share the amino acids, which suggests an overlap in the middle sequences.

Assemble the Sequence

We begin with the N-terminal Gly. Combine the fragments by starting with Gly, moving into Gly-Asp-Phe-Pro, then overlap Phe-Pro-Val with the middle section, linking to Val-Pro-Leu at the end, which closes with Leu at the C-terminal.

Key concepts

Peptide Fragmentation

Peptide fragmentation is an important method in understanding the structure of peptides. When a peptide is subjected to fragmentation, it breaks into smaller pieces, or fragments. These fragments provide insight into how the individual amino acids are arranged in the peptide. For the octapeptide in the exercise, we used fragments like Val-Pro-Leu and Gly-Asp-Phe-Pro to reconstruct the sequence.
Fragmentation can occur naturally, such as in acidic conditions, or through analytical techniques like mass spectrometry. In this exercise, chemical fragmentation helps to map out a possible sequence for the octapeptide, which is crucial when other methods cannot provide the complete structure.
Understanding peptide fragmentation is beneficial for identifying proteins and determining their sequences, as it reveals which amino acids are adjacent to each other and how they might overlap in different fragments.

Amino Acid Sequence

The amino acid sequence of a peptide is the precise order in which amino acids are linked together to form the peptide chain. This sequence determines the eventual shape and function of the peptide. In our octapeptide example, the goal is to identify the correct linear sequence of amino acids: Asp, Gly, Leu, Phe, Pro, and Val.
Knowing the sequence is critical as it dictates how a peptide interacts with other molecules. The sequence Gly-Asp-Phe-Pro, identified from fragmentation data, is part of this process. Each fragment helps in placing each amino acid at the right spot within the sequence. By layering the fragments together, we achieve the full peptide sequence with identified termini — Gly at the N-terminal and Leu at the C-terminal.
Correctly identifying sequences is key in understanding biochemical pathways, drug design, and protein synthesis.

Edman Degradation

Edman degradation is a method for sequencing amino acids in a peptide. It sequentially removes one amino acid at a time from the N-terminal end, allowing its identity to be determined without disrupting the overall peptide structure. In the given exercise, Edman degradation indicates that glycine is the N-terminal amino acid.
This technique is particularly useful for short peptides, and can be done repeatedly to determine each amino acid in the sequence. It systematically peels away amino acids, revealing the structure one at a time, which can be vital when piecing together an octapeptide.
Learning to use Edman degradation weaves into a broader skill of determining sequences, allowing scientists to uncover detailed information about peptides and proteins efficiently.

Chemical Hydrolysis

Chemical hydrolysis is a process that breaks down peptides by adding water to cleave peptide bonds. In the context of the octapeptide exercise, acidic hydrolysis was used to split the peptide into smaller fragments.
This method capitalizes on the susceptibility of certain peptide bonds to acidic or basic environments, leading to predictable breaks. The fragments generated, such as Val-Pro-Leu and Phe-Pro-Val, are analyzed to determine how the entire chain is organized.
Understanding hydrolysis is critical for peptide research as it enables scientists to deduce sequences from larger peptides. It gives insights into peptide stability and allows experiments that would otherwise be impossible due to the complexity of the whole chain.