Question

Contrasting isomers. Poly-L-leucine in an organic solvent such as dioxane is \(\alpha\) helical, whereas poly-L-isoleucine is not. Why do these amino acids with the same number and kinds of atoms have different helix-forming tendencies?

Short answer

Poly-L-leucine has a side chain that allows for alpha-helix formation due to less steric hindrance, whereas isoleucine's side chain prevents it.

Step-by-step solution

Understand Isomers

Isomers are compounds that share the same chemical formula but differ in the arrangement of atoms or spatial orientation. In this context, poly-L-leucine and poly-L-isoleucine have the same chemical composition but differ in the structure.

Analyze Side Chain Structures

Examine the side chains of leucine and isoleucine. Both have similar structures, but the placement of the methyl groups differs. Leucine has a side chain of isobutyl, while isoleucine's side chain is sec-butyl. This difference alters the physical properties of the molecules.

Consider Steric Hindrance

The differences in side chain branching between leucine and isoleucine affect steric hindrance. Isoleucine's bulkier side chain can interfere with the formation of a regular alpha-helix by causing steric clashes and making the structure less favorable compared to leucine.

Impact on Helix Formation

While both amino acids can form peptide chains, the spatial arrangement due to isoleucine's side chain makes helix formation less stable. In leucine, the side chain allows for better packing and hydrogen bonding in the helix, hence it easily forms an alpha-helix.

Summarize Structural Influence on Physical Properties

The arrangement of side chains in leucine and isoleucine explains the difference in helix-forming ability despite similar atomic composition. Leucine's structure supports the typical helical formation due to lower steric hindrance, unlike isoleucine.

Key concepts

Alpha-helix formation

In biochemistry, an alpha-helix is a common structural motif found in proteins. It is characterized by a coiled backbone and is stabilized by hydrogen bonds. These hydrogen bonds occur between the carbonyl oxygen of one amino acid and the amine hydrogen of another, four residues earlier in the sequence.

When it comes to forming an alpha-helix, the structural shape is highly influenced by the side chains of the constituent amino acids. These side chains can either facilitate or hinder the formation of the helix. Leucine, with its specific side chain structure, allows for stable hydrogen bonding and helix formation. The side chain's position permits the polypeptide chain to coil neatly into an alpha-helix.

Proteins that can easily form alpha-helices are typically more flexible and can fit into many different structural environments. Conversely, a lack of one means that the protein might end up with a different shape, allowing for diverse biological functions.

Amino acid side chains

Amino acids are the building blocks of proteins, with each possessing a unique side chain that influences the protein's structural properties. The side chain of an amino acid can significantly affect how it interacts with other molecules, including other amino acids in a polypeptide chain.

For leucine and isoleucine, the principal difference lies in their side chains. Both have isomeric forms but their side chains vary in branching. Leucine has an isobutyl side chain, while isoleucine possesses a sec-butyl side chain. This small distinction affects how closely these side chains can pack together in a protein structure, which is crucial for the stability of the alpha-helix.

While leucine's side chain promotes smooth helix formation, isoleucine's bulkier structure can disrupt the helix-forming capability due to less efficient packing and increased steric clashes. Thus, the side chain configurations of amino acids are fundamental in determining protein structure.

Steric hindrance

Steric hindrance in proteins refers to the restriction of molecular motion due to the presence of bulky groups, which can dramatically influence molecular conformation and stability.

In the case of leucine versus isoleucine, steric hindrance plays a crucial role in their differing abilities to form an alpha-helix. Isoleucine’s sec-butyl side chain introduces more steric hindrance compared to leucine's isobutyl side chain. This increased bulkiness interferes with the regular arrangement needed for alpha-helix formation.

In scenarios where steric hindrance is pronounced, the protein may not readily adopt the traditional helical structure, limiting its flexibility and potential functions. By understanding the implications of steric hindrance, we gain insights into protein folding, stability, and its eventual biological activity.