ProfessorRobinLeatherbarrow

McBride JD, Freeman HN, Watson EM, Leatherbarrow RJet al., 2000, Chymotrypsin inhibitors identified from a second-generation template assisted combinatorial peptide library, Proceedings of the 6th international symposium on solid phase synthesis and combinatorial chemical libraries, Editors: Epton, Publisher: Mayflower Scientific Press, ISBN: 9780951573532

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McNee JJ, Wang FS, Leatherbarrow RJ, 1999, Expression and secretion of biologically active CMTI I in <i>Saccharomyces cerevisiae</i>, PROTEIN AND PEPTIDE LETTERS, Vol: 6, Pages: 351-358, ISSN: 0929-8665

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• Citations: 1

McBride JD, Freeman HNM, Leatherbarrow RJ, 1999, Selection of human elastase inhibitors from a conformationally-constrained combinatorial peptide library, EUROPEAN JOURNAL OF BIOCHEMISTRY, Vol: 266, Pages: 403-412, ISSN: 0014-2956

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• Citations: 43

Leatherbarrow RJ, Edwards PR, 1999, Analysis of molecular recognition using optical biosensors, CURRENT OPINION IN CHEMICAL BIOLOGY, Vol: 3, Pages: 544-547, ISSN: 1367-5931

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• Citations: 47

Gariani T, McBride JD, Leatherbarrow RJ, 1999, The role of the P₂′ position of Bowman-Birk proteinase inhibitor in the inhibition of trypsin -: Studies on P₂′ variation in cyclic peptides encompassing the reactive site loop, BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY, Vol: 1431, Pages: 232-237, ISSN: 0167-4838

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• Citations: 40

McBride JD, Freeman N, Leatherbarrow RJ, 1999, Selection of human elastase inhibitors from a conformationally-constrained combinatorial peptide library, Innovations and perspectives in solid phase synthesis and combinatorial libraries 1998, Editors: Epton, Publisher: Mayflower Scientific Press, Pages: 167-172, ISBN: 9780952701132

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McBride JD, Freeman N, Domingo GJ, Leatherbarrow RJet al., 1999, Selection of proteinase inhibitors from a conformationally-constrained combinatorial peptide library, Innovations and perspectives in solid phase synthesis and combinatorial libraries 1998, Editors: Epton, Publisher: Mayflower Scientific Press, Pages: 465-468, ISBN: 9780952701118

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Edwards PR, Maule CH, Leatherbarrow RJ, Winzor DJet al., 1998, Second-order kinetic analysis of IAsys biosensor data: Its use and applicability, ANALYTICAL BIOCHEMISTRY, Vol: 263, Pages: 1-12, ISSN: 0003-2697

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• Citations: 39

McBride JD, Brauer AB, Nievo M, Leatherbarrow RJet al., 1998, The role of threonine in the P2 position of Bowman-Birk proteinase inhibitors: studies on P2 variation in cyclic peptides encompassing the reactive site loop., J Mol Biol, Vol: 282, Pages: 447-458, ISSN: 0022-2836

Previously, we have described a template-assisted combinatorial peptide library based on the anti-tryptic reactive site loop of a Bowman-Birk inhibitor (BBI). Sequences that displayed inhibitory activity re-directed towards chymotrypsin were found to have a consensus binding motif, with their most striking feature being that exclusively threonine was found at the P2 position. The present study investigates the reason for this surprising specificity by maintaining the binding motif but systematically varying the P2 residue. From analysis of 26 variants, it is found that the requirements for inhibitory activity at P2 are finely tuned, and in agreement with the library work, threonine at P2 provides optimal inhibition. In addition, peptides with threonine at P2 are significantly less susceptible to hydrolysis. Examination of all available BBI sequences shows that threonine is very highly conserved at P2, which implies that the functional requirement extends to the full-length BBI protein. Our results are consistent with a dual requirement for hydrophobic recognition within the S2 pocket and maintenance of an inhibitory conformation via hydrogen bonding within the reactive-site loop. As the isolated peptide loop reproduces the active region of full-length BBI, these results explain why threonine is well conserved at P2 in this class of inhibitor. Furthermore, they illustrate that proteinase inhibitor specificity can have characteristics that are not easily predicted from information on the substrate preferences of a proteinase.

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McBride JD, Brauer ABE, Nievo M, Leatherbarrow RJet al., 1998, The role of threonine in the P₂ position of bowman-birk proteinase inhibitors:: Studies on P₂ variation in cyclic peptides encompassing the reactive site loop, JOURNAL OF MOLECULAR BIOLOGY, Vol: 282, Pages: 447-457, ISSN: 0022-2836

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• Citations: 43

Hasan Z, Leatherbarrow RJ, 1998, A study of the specificity of barley chymotrypsin inhibitor 2 by cysteine engineering of the P1 residue, BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY, Vol: 1384, Pages: 325-334, ISSN: 0167-4838

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• Citations: 3

Foord RL, Leatherbarrow RJ, 1998, Effect of osmolytes on the exchange rates of backbone amide protons in proteins, BIOCHEMISTRY, Vol: 37, Pages: 2969-2978, ISSN: 0006-2960

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• Citations: 51

Leatherbarrow RJ, 1998, GraFit version 4.0. Data Analysis and Graphics program for the IBM PC., Staines, UK, Publisher: Erithacus Software

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Hasan Z, Leatherbarrow RJ, 1997, Introduction of trypsin specificity into chymotrypsin inhibitor II, PROTEIN AND PEPTIDE LETTERS, Vol: 4, Pages: 335-342, ISSN: 0929-8665

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Gariani T, Leatherbarrow RJ, 1997, Stability of protease inhibitors based on the Bowman-Birk reactive site loop to hydrolysis by proteases, JOURNAL OF PEPTIDE RESEARCH, Vol: 49, Pages: 467-475, ISSN: 1397-002X

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• Citations: 29

Edwards PR, Leatherbarrow RJ, 1997, Determination of association rate constants by an optical biosensor using initial rate analysis, ANALYTICAL BIOCHEMISTRY, Vol: 246, Pages: 1-6, ISSN: 0003-2697

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• Citations: 65

Edwards PR, Lowe PA, Leatherbarrow RJ, 1997, Ligand loading at the surface of an optical biosensor and its effect upon the kinetics of protein-protein interactions, JOURNAL OF MOLECULAR RECOGNITION, Vol: 10, Pages: 128-134, ISSN: 0952-3499

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• Citations: 44

McBride JD, Brauer ABE, Nievo M, Leatherbarrow RJet al., 1997, Functional Requirement for a Threonine in the P2 Position of a Cyclic Peptide Mimetic of a Bowman-Birk Proteinase Inhibitor, Innovations and Perspectives in Solid Phase Synthesis and Combinatorial Libraries 1998, Editors: Epton, Epton, Publisher: Mayflower Scientific Press, Pages: 341-344, ISBN: 9780952701132

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Brauer ABE, McBride JD, Nievo M, Matthews SJ, Cooke RM, Leatherbarrow RJet al., 1997, How small is a protein allowed to be? Three dimensional structure-activity relationship in mini protease inhibitors based on larger protein structures, 26th German Chemical Society Annual General Meeting and 100 years of the Austrian Chemical Society, Publisher: German Chemical Society Press

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Holmes DIR, Mantafounis D, Ward WHJ, Leatherbarrow RJet al., 1996, Bacteriophage display of chymotrypsin inhibitor 2, PROTEIN AND PEPTIDE LETTERS, Vol: 3, Pages: 415-422, ISSN: 0929-8665

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• Citations: 2

Gill A, Leatherbarrow RJ, Hoare M, PollardKnight DV, Lowe PA, Fortune DHet al., 1996, Analysis of kinetic data of antibody-antigen interaction from an optical biosensor by exponential curve fitting, JOURNAL OF BIOTECHNOLOGY, Vol: 48, Pages: 117-127, ISSN: 0168-1656

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• Citations: 20

McBride JD, Freeman N, Domingo GJ, Leatherbarrow RJet al., 1996, Selection of chymotrypsin inhibitors from a conformationally-constrained combinatorial peptide library, JOURNAL OF MOLECULAR BIOLOGY, Vol: 259, Pages: 819-827, ISSN: 0022-2836

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• Citations: 67

McBride JD, Harbeck B, Leatherbarrow RJ, 1996, Resin-coupled cyclic peptides as proteinase inhibitors, PROTEIN AND PEPTIDE LETTERS, Vol: 3, Pages: 193-198, ISSN: 0929-8665

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• Citations: 3

EDWARDS PR, GILL A, POLLARDKNIGHT DV, HOARE M, BUCKLE PE, LOWE PA, LEATHERBARROW RJet al., 1995, KINETICS OF PROTEIN-PROTEIN INTERACTIONS AT THE SURFACE OF AN OPTICAL BIOSENSOR, ANALYTICAL BIOCHEMISTRY, Vol: 231, Pages: 210-217, ISSN: 0003-2697

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• Citations: 153

DOMINGO GJ, LEATHERBARROW RJ, FREEMAN N, PATEL S, WEIR Met al., 1995, SYNTHESIS OF A MIXTURE OF CYCLIC-PEPTIDES BASED ON THE BOWMAN-BIRK REACTIVE-SITE LOOP TO SCREEN FOR SERINE-PROTEASE INHIBITORS, INTERNATIONAL JOURNAL OF PEPTIDE AND PROTEIN RESEARCH, Vol: 46, Pages: 79-87, ISSN: 0367-8377

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• Citations: 48

GREAGG MA, BRAUER ABE, LEATHERBARROW RJ, 1994, EXPRESSION AND KINETIC CHARACTERIZATION OF BARLEY CHYMOTRYPSIN INHIBITORS 1A AND 1B, BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, Vol: 1222, Pages: 179-186, ISSN: 0167-4889

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• Citations: 11

Leatherbarrow RJ, 1994, FASTfit: Biosensor interaction analysis software, Cambridge, Publisher: Fisons Applied Sensor Technology

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MANTAFOUNIS D, HOLMES DIR, LEATHERBARROW RJ, 1994, CHYMOTRYPSIN INHIBITOR-2 (C-12) DISPLAY ON THE SURFACE OF BACTERIOPHAGE, JOURNAL OF CELLULAR BIOCHEMISTRY, Pages: 157-157, ISSN: 0730-2312

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Leatherbarrow RJ, Greagg MA, Domingo GJ, Gariani Tet al., 1994, Mechanistic Studies of Plant Proteinase Inhibitors, Advances in the Chemistry of Insect Control III, Editors: Briggs, Publisher: Royal Society of Chemistry

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GARIANI T, LEATHERBARROW RJ, 1994, STUDY OF DIFFERENT BASED BOWMAN AND BIRK PEPTIDES INHIBITORS, JOURNAL OF CELLULAR BIOCHEMISTRY, Pages: 155-155, ISSN: 0730-2312

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