How Long to Read The Importance of Hydrogen-bonding Edges and Hydrophobic Surfaces in Inhibiting Amyloid Aggregation

How Long Does it Take to Read The Importance of Hydrogen-bonding Edges and Hydrophobic Surfaces in Inhibiting Amyloid Aggregation?

It takes the average reader 4 hours and 24 minutes to read The Importance of Hydrogen-bonding Edges and Hydrophobic Surfaces in Inhibiting Amyloid Aggregation by Jing Zheng

Assuming a reading speed of 250 words per minute. Learn more

Description

Layered parallel beta-sheets are central to protein and peptide aggregation in numerous amyloid-related diseases. We have used a tau-protein-derived hexapeptide, AcPHF6, as a model system to study the aggregation and inhibition processes which involve layered parallel beta-sheet structures. This dissertation describes the studies of a series of macrocyclic beta-sheet peptides that inhibit the aggregation of AcPHF6. Macrocycles 1 containing the pentapeptide VQIVY in the "upper" strand delay and suppress the onset of AcPHF6 aggregation. Inhibition is particularly pronounced in macrocycles 1a, 1d, and 1f, in which the two residues in the "lower" strand provide a pattern of hydrophobicity and hydrophilicity that matches that of the pentapeptide "upper" strand. Inhibition varies strongly with the concentration of these macrocycles, suggesting that it is cooperative. On the basis of these studies, a model is proposed in which the AcPHF6 amyloid grows as a layered pair of beta-sheets and in which growth is blocked by a pair of macrocycles that cap the growing paired hydrogen-bonding edges. We then systematically studied the macrocycles and found that positions R1, R3, and R7 are especially sensitive to mutations. Reducing hydrophobicity at these positions substantially diminishes inhibition. Although position R5 is not sensitive to mutations that reduce hydrophobicity, it is sensitive to mutations that increase hydrophobicity. Enhanced hydrophobicity at this position substantially enhances inhibition. These studies establish that the hydrophobic surface comprising residues R1, R3, and R7 is crucial to the inhibition process and that the residue R5, which shares this surface, is also important. Collectively, these studies demonstrate the importance of hydrogen-bonding edges and hydrophobic surfaces in inhibiting amyloid aggregation. Attempts to synthesize covalently-linked macrocyclic beta-sheet peptides in order to promote cooperativity are also described in the Dissertation.

How long is The Importance of Hydrogen-bonding Edges and Hydrophobic Surfaces in Inhibiting Amyloid Aggregation?

The Importance of Hydrogen-bonding Edges and Hydrophobic Surfaces in Inhibiting Amyloid Aggregation by Jing Zheng is 262 pages long, and a total of 66,024 words.

This makes it 88% the length of the average book. It also has 81% more words than the average book.

How Long Does it Take to Read The Importance of Hydrogen-bonding Edges and Hydrophobic Surfaces in Inhibiting Amyloid Aggregation Aloud?

The average oral reading speed is 183 words per minute. This means it takes 6 hours to read The Importance of Hydrogen-bonding Edges and Hydrophobic Surfaces in Inhibiting Amyloid Aggregation aloud.

What Reading Level is The Importance of Hydrogen-bonding Edges and Hydrophobic Surfaces in Inhibiting Amyloid Aggregation?

The Importance of Hydrogen-bonding Edges and Hydrophobic Surfaces in Inhibiting Amyloid Aggregation is suitable for students ages 12 and up.

Note that there may be other factors that effect this rating besides length that are not factored in on this page. This may include things like complex language or sensitive topics not suitable for students of certain ages.

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