Author

Aaron Langdon

Date of Award

2009

Degree Type

Thesis

Degree Name

Master of Science

Program

Biochemistry

Supervisor

Drs. Harvey Goldberg

Second Advisor

Graeme Hunter

Abstract

Bone sialoprotein, because of its affinity for the triple-helical type I collagen molecule and increased HA-nucleation potency upon binding collagen in vitro, is postulated to interact with type I collagen in vivo to initiate bone formation. Although the collagen-binding region of BSP has been located, the area of collagen involved in this interaction remains unknown. Through chemically cross-linking BSP to type I collagen, this region can be precisely mapped. The purpose of this study is to develop the reagents and protocols necessary for the covalent attachment of BSP to collagen, thereby creating

the possibility of locating the BSP-binding region of collagen in the future. Five prokaryotically expressed, single-cysteine mutants of the rat BSP (1-100) peptide were expressed, purified, and conjugated to the sulfhydryl reactive, photoactivatable cross- linking reagents BPM, APB and APDP. These conjugates were incubated with type I collagen extracted from rat tail tendons, and irradiated by UV light to induce cross-link formation. SDS-PAGE and Western blot were used to detect and characterize cross- linked complexes, including covalently linked aggregates of rBSP (1-100). Using APDP, successful cross-links to collagen were detected with four ofthe five rBSP (1-100) mutants. Using the protocols and reagents developed in this study, it will be possible to better characterize the BSP-collagen interaction and its role in early mineral formation

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