Problem 88 - General Chemistry: Principles and Modern Applications

Question

Upon complete hydrolysis of a pentapeptide, the following amino acids are obtained: valine, phenylalanine, glycine, cysteine, and tyrosine. Partial hydrolysis yields the following fragments: Val-Phe; Cys-Gly; Cys-Val-Phe; Tyr- Phe. If glycine is the N-terminal acid, what is the sequence of amino acids in the polypeptide?

Step-by-Step Solution

Answer

The sequence of the amino acids in the polypeptide is Gly-Cys-Val-Phe-Tyr.

Step 1: Identification of Terminal Amino Acids

Firstly, identify the N-terminal and C-terminal acids. From the exercise, it is known that glycine is the N-terminal acid. Also in the fragment Tyr-Phe, tyrosine cannot be an immediate neighbor to any other amino acid, therefore tyrosine must be the C-terminal amino acid.

Step 2: Arrangement of Partial Hydrolysis Fragments

Next, arrange the fragments from partial hydrolysis. Using the fragments obtained, the sequence glycine (N-terminal) - cysteine - valine - phenylalanine - tyrosine (C-terminal) can be formed. This takes into account all fragments: Gly-Cys comes from Cys-Gly, Cys-Val-Phe from Cys-Val-Phe, and makes sense in the context of Tyr-Phe as well.

Step 3: Formation of Polypeptide

Now the final polypeptide can be assembled. The final amino acid sequence is Gly-Cys-Val-Phe-Tyr. This sequence includes all partial fragments and considers glycine as the N-terminal and tyrosine as the C-terminal acid.

Key Concepts

Hydrolysis of Peptides

Hydrolysis of peptides is a fundamental biochemical process. It involves breaking down peptide bonds in peptides to release individual amino acids. This is achieved through the addition of water molecules. The process is crucial for analyzing and understanding protein structures.
When a peptide, like a pentapeptide, undergoes complete hydrolysis, it is broken into its constituent amino acids. For instance, if a pentapeptide yields valine, phenylalanine, glycine, cysteine, and tyrosine, this indicates these amino acids were originally linked in a sequence.

• Complete hydrolysis breaks all peptide bonds, providing the composition of the original peptide.
• Partial hydrolysis yields larger peptide fragments, offering clues about the original sequence.

By analyzing these fragments, we can reconstruct the amino acid sequence of the peptide. This is how scientists deduce the arrangement of amino acids in a sequence like Gly-Cys-Val-Phe-Tyr.

N-terminal Amino Acid

The N-terminal amino acid is the first amino acid in a peptide or protein. It is crucial for determining the directionality of peptide synthesis and plays a significant role in protein function. Knowing the N-terminal amino acid helps deduce the overall sequence of a peptide during analysis. In the example, glycine is identified as the N-terminal amino acid. This piece of information is essential because:

• The N-terminal sets the start of the sequence direction.
• It determines the reading frame of a polypeptide sequence.

Upon partial hydrolysis, one can often find fragments that emphasize N-terminal to downstream sequences, confirming parts of the sequence arrangement. Pinpointing the N-terminal as glycine confirms that it starts the sequence, leading to correctly deducing the arrangement as Gly-Cys-Val-Phe-Tyr.

Polypeptide Arrangement

Understanding polypeptide arrangement is key in deriving the functional aspects of proteins. Peptides are composed of amino acids linked in a specific sequence. This arrangement determines the protein's properties and function. In the exercise, correctly arranging the fragments acquired through partial hydrolysis is crucial. Upon knowing the N-terminal (glycine), fragments like Val-Phe, Cys-Gly and Tyr-Phe are aligned to piece together the overall sequence:

• Identify overlapping sequences, such as fragments that share common amino acids, to align them correctly.
• Verify continuity, ensuring that fragment ends and beginnings make logical sense in succession.
• Consider intra-fragment relationships; for example, Cys-Gly implies Gly follows Cys in the sequence.

With this method, you align the fragments sequentially to recreate the correct polypeptide structure, Gly-Cys-Val-Phe-Tyr, mirroring the exact arrangement in nature.