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1. Computer-aided design and physiological testing of a luteinising hormone-releasing hormone analogue for 'adjuvant-free' immunocastration

Author

David J. Ward, Robert V. Fishleigh, Barry Robson, and Christopher Morrison

Subjects
Purified protein derivative, Male, medicine.medical_specialty, medicine.medical_treatment, Biophysics, Molecular Conformation, Biology, Peptide hormone, Active immunization, Tuberculin, Biochemistry, Gonadotropin-Releasing Hormone, chemistry.chemical_compound, Structural Biology, Internal medicine, Structure prediction, Testis, Genetics, medicine, Animals, Computer Simulation, Molecular Biology, Autoantibodies, Immunological castration, Molecular design, Luteinising hormone releasing hormone, Luteinising hormone-releasing hormone, Cell Biology, Rats, Castration, Endocrinology, chemistry, Models, Chemical, Immunization, Adjuvant, BCG vaccine, Conjugate
Abstract

An analogue of LHRH containing an extension of Gly-Cys at the carboxyl-terminus has been designed to permit reproducible coupling to a suitably modified carrier via a thioether bond. Potential energy calculations indicated that this analogue adopted a conformation in solution virtually identical to the type II′ turn around Gly-6—Leu-7 predicted for native LHRH. Intradermal administration of a conjugate of this analogue with purified protein derivative of tuberculin to male rats previously primed with BCG vaccine rapidly led to complete testicular regression. This adjuvant-free immunisation protocol may represent an alternative to castration for the veterinary control of reproductive function.

Published
1987

2. Studies on rationales for an expert system approach to the interpretation of protein sequence data. Preliminary analysis of the human epidermal growth factor receptor

Author

Robert V. Fishleigh, Barry Robson, Paul W. Finn, and Jean Garnier

Subjects
Models, Molecular, Protein Conformation, Biophysics, Expert Systems, Computational biology, computer.software_genre, Bioinformatics, Biochemistry, Homology (biology), Preliminary analysis, Protein sequencing, Structural Biology, Epidermal growth factor, Structure prediction, Genetics, Humans, Epidermal growth factor receptor, Amino Acid Sequence, Cysteine, Molecular Biology, Protein secondary structure, Expert system, biology, Proteins, Cell Biology, Homology, ErbB Receptors, Membrane protein, biology.protein, computer, Insulin receptor
Abstract

The molecular modelling of larger proteins benefits from a preliminary analysis of the sequence to identify regions of potential structural and functional importance. In this study the sequence of the epidermal growth factor receptor has been analysed using a variety of established methods and novel procedures developed for the study of weak internal and external homologies and for the use of homologous sequences in the prediction of secondary and super-secondary structures. The procedures explored here are potentially suitable for incorporation into an expert system for the initial investigation of protein sequence data.

Published
1987

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