Lengyel, George
(2012)
Designing Methodology for the Incorporation of Beta-Amino Acids into Protein Tertiary Structures.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
The goal of this project is to explore methodologies applicable to introducing β-amino acid residues into
natural protein sequences with well-defined tertiary structures while maintaining the folded structure of
these natural sequences. Hybrid α/β-peptides synthesized with β-amino acids have additional rotational
freedom of their backbone and also have increased resistance to proteolysis relative to natural α-peptides.
16 unnatural β-amino acids with varied stereochemistry and torsional restraints were synthesized using a
variety of published literature methods. A peptide model system known to fold into a β-hairpin secondary
structure in aqueous solution was chosen for substitution with the unnatural residues at two positions.
Using Fmoc solid-phase peptide synthesis, 16 hybrid α/β-peptides as well as 16 unfolded control peptides
were synthesized and studied by 2D NMR. Using the NMR data obtained from this study, the mutant
peptides were analyzed for indications of folded population. Three peptides showed a high degree of
folded population: those including a β3
-amino acid and two including the enantiomers of a trans-
disubstituted-β2,3
-amino acid. NOE-derived distance restraints were established and high-resolution 3D
structures of these peptides were calculated. Using these structures, it was found that the peptide
substituted with (2R, 3S)-3-amino-2,4-dimethylpentanoic acid most closely emulated the hairpin structure
of the model system. Currently, work is ongoing to determine the effect of side-chain functionalization
and substitution pattern on the folding of larger protein systems.
Share
| Citation/Export: |
|
| Social Networking: |
|
Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
|
| Date: |
18 January 2012 |
| Date Type: |
Publication |
| Defense Date: |
11 November 2011 |
| Approval Date: |
18 January 2012 |
| Submission Date: |
1 December 2011 |
| Access Restriction: |
5 year -- Restrict access to University of Pittsburgh for a period of 5 years. |
| Number of Pages: |
127 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Dietrich School of Arts and Sciences > Chemistry |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
amino acid, peptide, beta, residue, tertiary structure, secondary structure, beta sheet |
| Date Deposited: |
18 Jan 2012 19:34 |
| Last Modified: |
18 Jan 2017 06:15 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/10618 |
Metrics
Monthly Views for the past 3 years
Plum Analytics
Actions (login required)
 |
View Item |
![[feed]](/images/feed-icon-32x32.png){kind=icon}