Probing epidermal growth factor receptor recognition
Probing epidermal growth factor receptor recognition
The role of the B-loop region of epidermal growth factor (EGF) in mediating the recognition of this protein by its cellular receptor has been investigated. A review of the importance of EGF-family growth factors in the control of cell division and their probable involvement in tumour growth is presented. The discovery, occurrence and biological activity of EGF is discussed, and the relationship of its primary, secondary and tertiary structure to biological function is presented. In particular, a model in which the B- and C-loops of the protein form a hydrophobic cavity essential for interaction with the receptor has been developed. The synthesis of a number of linear peptides based on the B-loop sequence of human EGF has been achieved, together with cyclic derivatives obtained by the formation of intra-molecular disulphide bonds. The latter compounds were anticipated to better resemble the β-sheet structure of the B-loop in EGF. These peptides were used in biological assays of mitogenesis and the results are presented. No mitogenic activity was evident in all cases and possible explanations are discussed. Replacement of the disulphide links by a β-turn peptidomimetic was investigated, and the successful synthesis of a suitably functionalised non-natural amino acid is presented.
University of Southampton
1990
Hill, David Neale
(1990)
Probing epidermal growth factor receptor recognition.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
The role of the B-loop region of epidermal growth factor (EGF) in mediating the recognition of this protein by its cellular receptor has been investigated. A review of the importance of EGF-family growth factors in the control of cell division and their probable involvement in tumour growth is presented. The discovery, occurrence and biological activity of EGF is discussed, and the relationship of its primary, secondary and tertiary structure to biological function is presented. In particular, a model in which the B- and C-loops of the protein form a hydrophobic cavity essential for interaction with the receptor has been developed. The synthesis of a number of linear peptides based on the B-loop sequence of human EGF has been achieved, together with cyclic derivatives obtained by the formation of intra-molecular disulphide bonds. The latter compounds were anticipated to better resemble the β-sheet structure of the B-loop in EGF. These peptides were used in biological assays of mitogenesis and the results are presented. No mitogenic activity was evident in all cases and possible explanations are discussed. Replacement of the disulphide links by a β-turn peptidomimetic was investigated, and the successful synthesis of a suitably functionalised non-natural amino acid is presented.
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Published date: 1990
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Local EPrints ID: 460633
URI: http://eprints.soton.ac.uk/id/eprint/460633
PURE UUID: 21c578a5-9ebc-4389-8696-9750839b7257
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Date deposited: 04 Jul 2022 18:26
Last modified: 04 Jul 2022 18:26
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Author:
David Neale Hill
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