The Rational Design of Coiled-Coil Peptides towards Understanding Protein-Crystal Interactions and Amorphous-to-Crystalline Transitions

This dissertation reflects efforts to the combine biomineralization research and rational peptide design using the coiled-coil peptide motif and calcium hydrogen phosphate dihydrate (CaHPO4 x 2H2O), commonly known as brushite. Coiled-coils were designed to alter the complete growth pathway of brushite beginning with an amorphous precursor and resulting in a modified crystalline state. Both the designed chemical character and the secondary structure of the coiled-coil peptides were found to be important factors in controlling the growth pathway of brushite and the morphology of the final crystalline state. The impact of peptide secondary structure on the growth of brushite was studied by comparing the effects of a well structured coiled-coil peptide (AQQ5E) to a structurally disordered analog with nearly identical chemical properties (RCA5E) on the final crystal morphology. Typically, brushite crystals formed in the absence of growth modifying agents display {100}, {010}, {10-2} and {10-1} crystal faces. However, in the presence of AQQ5E the growth of the {10-2} faces were selectively inhibited in the final crystal product. Conversely, crystals grown in the presence of RCA5E adopted a wide variety of morphologies without a preferred means of crystal modification. Computational analysis demonstrated how the two peptides may interact with the different crystal faces of brushite and provided insight for explaining this behavior. In another study, a series of coiled-coil peptides with similar secondary structure yet increasing acidic amino acid content were used to determine the impact of designed peptides on amorphous-to-crystalline transition of brushite leading up to the final crystalline state. In the absence of peptides, the amorphous-to-crystalline transition of brushite occurred rapidly with the final crystalline state being achieved within several hours. However, the addition of acidic peptides prolonged this process over several days and allowed for the study and characterization of a novel amorphous-crystalline, hybrid phase of brushite adopting a ribbon-like morphology. Studying the formation and stability of the intermediate brushite phase in the presence of structurally similar yet chemically distinctive peptides suggested that both secondary structure and chemical composition impact the manner in which peptides interact with amorphous and crystalline materials.

Name thesis:degree_name

Doctor of Philosophy (Ph.D.)

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

Photochemical Sciences

Grantor dc:publisher

Bowling Green State University

Year dc:date

2013

Author dc:creator

• Chang, Eric P.

Contributors dc:contributor

• Ogawa, Michael

• Chemistry
• biomineralization
• designed peptides
• coiled coils
• secondary structure
• peptide-crystal interactions
• amorphous-to-crystalline transitions

Statement dc:rights

• unrestricted
• This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.

Language dc:language

English

Repository record dc:identifier

http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1363258701

OAI identifier oai:identifier

oai:etd.ohiolink.edu:bgsu1363258701