Structures and related properties of helical, disulfide-stabilized peptides

PDF Version Also Available for Download.

Description

The three dimensional structure of several peptides were determined by NMR spectroscopy and distance geometry calculations. Each peptide formed a predictable, rigid structure, consisting of an {alpha}-helix, a {open_quotes}scaffold{close_quotes} region which packed along one face of the helix, and two disulfide bridges which covalently connect the helix and scaffold regions. The peptide Apa-M5 was designed to constrain the M5 peptide from MLCK in a helical geometry using the apamin disulfide scaffold. This scaffold constrains the N- terminal end of the helix with two disulfide bridges and a reverse turn. Like the M5 peptide, Apa-M5 was found to bind calmodulin in ... continued below

Physical Description

206 p.

Creation Information

Pagel, M. D. November 1, 1993.

Context

This thesis or dissertation is part of the collection entitled: Office of Scientific & Technical Information Technical Reports and was provided by UNT Libraries Government Documents Department to Digital Library, a digital repository hosted by the UNT Libraries. More information about this document can be viewed below.

Who

People and organizations associated with either the creation of this thesis or dissertation or its content.

Author

  • Pagel, M. D. Univ. of California, Berkeley, CA (United States). Dept. of Chemistry

Sponsor

Publisher

Provided By

UNT Libraries Government Documents Department

Serving as both a federal and a state depository library, the UNT Libraries Government Documents Department maintains millions of items in a variety of formats. The department is a member of the FDLP Content Partnerships Program and an Affiliated Archive of the National Archives.

Contact Us

What

Descriptive information to help identify this thesis or dissertation. Follow the links below to find similar items on the Digital Library.

Description

The three dimensional structure of several peptides were determined by NMR spectroscopy and distance geometry calculations. Each peptide formed a predictable, rigid structure, consisting of an {alpha}-helix, a {open_quotes}scaffold{close_quotes} region which packed along one face of the helix, and two disulfide bridges which covalently connect the helix and scaffold regions. The peptide Apa-M5 was designed to constrain the M5 peptide from MLCK in a helical geometry using the apamin disulfide scaffold. This scaffold constrains the N- terminal end of the helix with two disulfide bridges and a reverse turn. Like the M5 peptide, Apa-M5 was found to bind calmodulin in a Ca{sup 2+}-dependent 1:1 stoichiometry. However, the dissociation constant of the (Apa-M5)-calmodulin complex, 107 nM, was 100-fold higher than the dissociation constant of the M5-calmodulin complex. This difference was due to a putative steric overlap between the Apa-M5 scaffold and calmodulin. The peptide Apa-Cro was designed to replace the large structural protein matrix of {lambda} Cro with the apamin disulfide scaffold. However, Apa-Cro did not bind the consensus DNA operator half-site of {lambda} Cro, probably due to a steric overlap between the Apa-Cro disulfide framework and the DNA. The amino acid sequence of the scaffold-disulfide bridge arrangement of the peptide Max was derived from the core sequence of scyllatoxin, which contains an {alpha}-helix constrained at the C-terminal end by two disulfide bridges and a two-stranded {beta}sheet scaffold. Max was shown to fold with >84% yield to form a predictable, stable structure that is similar to scyllatoxin. The folding and stability properties of Max make this scaffold and disulfide bridge arrangement an ideal candidate for the development of hybrid sequence peptides. The dynamics of a fraying C-terminal end of the helix of the peptide Apa-AlaN was determined by analysis of {sup 15}N NMR relaxation properties.

Physical Description

206 p.

Notes

OSTI as DE94005210; Paper copy available at OSTI: phone, 865-576-8401, or email, reports@adonis.osti.gov

Source

  • Other Information: TH: Thesis (Ph.D.)

Language

Identifier

Unique identifying numbers for this document in the Digital Library or other systems.

  • Other: DE94005210
  • Report No.: LBL--34903
  • Grant Number: AC03-76SF00098
  • Office of Scientific & Technical Information Report Number: 10115409
  • Archival Resource Key: ark:/67531/metadc1272776

Collections

This document is part of the following collection of related materials.

Office of Scientific & Technical Information Technical Reports

Reports, articles and other documents harvested from the Office of Scientific and Technical Information.

Office of Scientific and Technical Information (OSTI) is the Department of Energy (DOE) office that collects, preserves, and disseminates DOE-sponsored research and development (R&D) results that are the outcomes of R&D projects or other funded activities at DOE labs and facilities nationwide and grantees at universities and other institutions.

What responsibilities do I have when using this thesis or dissertation?

When

Dates and time periods associated with this thesis or dissertation.

Creation Date

  • November 1, 1993

Added to The UNT Digital Library

  • Oct. 12, 2018, 6:44 a.m.

Description Last Updated

  • Nov. 27, 2018, 3:27 p.m.

Usage Statistics

When was this document last used?

Yesterday: 0
Past 30 days: 2
Total Uses: 2

Interact With This Thesis Or Dissertation

Here are some suggestions for what to do next.

Start Reading

PDF Version Also Available for Download.

International Image Interoperability Framework

IIF Logo

We support the IIIF Presentation API

Pagel, M. D. Structures and related properties of helical, disulfide-stabilized peptides, thesis or dissertation, November 1, 1993; California. (https://digital.library.unt.edu/ark:/67531/metadc1272776/: accessed March 21, 2019), University of North Texas Libraries, Digital Library, https://digital.library.unt.edu; crediting UNT Libraries Government Documents Department.