Our group designs, synthesizes and studies the chemistry of molecular tools used in biochemistry, biotechnology and cell and molecular biology. Of most interest are cross-linking reagents, photo activated cross-link reagents and selective cleavage agents for proteins. Cross-linking reagents are bifunctional molecules that bridge between residues on a single protein or between residues on separate, but associated protein chains. The chemistry also provides pathways for the "tethering" of chemical identifiers to proteins and to assemble enzymes, proteins and antibodies on solid supports.
The research group has pioneered the chemistry of both mobile protein cross-link and unique photo-activatable cross-linking reagents. Equilibrium transfer alkylation cross-links [acronym:ETAC] reagents allow the linking of residues on protein chains in either an intra- or inter-molecular fashion, yet the reagents still retain a mobile, transferable character. They can transfer from one protein residue to another or even to another protein through a cascade of consecutive Michael/retro-Michael reactions. Thus, the reagents have the ability to "walk", "skip", "jump" or "pivot" from one residue to another within the protein framework or protein aggregate architecture through a series of consecutive conjugate additions. The linked residues identify the distances and relationships of the sites in the proteins. By the incremental increase in the length of the bridging reagents, rigid molecular yardsticks are created that allow the measurement between different distant sites in proteins. Such yardstick-like molecules can also be used in the construction of unique large ring structures and in the construction of molecular architectures for the identification of molecular recognition elements.
S. Mitra and R.G. Lawton "Reagents for the Cross-linking of Proteins by Equilibrium Transfer Alkylation," J. Am. Chem. Soc. (1979), 101, 3097. V.S. Goodfellow, M. Setteneri and R.G. Lawton "p-Nitrophenyl 3-diazopyruvate and Diazopyruvamides. A New Family of Photoactivatable Cross-linking Bioprobes" Biochemistry 1989, 28, 6346. F.A. Liberatore, R.D. Comeau, J. M. McKearin, D.A. Pearson, B.Q. Belonga, S.J. Brocchini, J. Kath, T. Phillips, K. Oswell and R.G. Lawton, "Site-Directed Modification and Cross-linking of a Monoclonal Antibody with Equilibrium Transfer Alkylating Cross-link Reagents" Bioconjugate Chemistry 1990,1, (Jan-Feb) 36.
J.M. Taylor, G.G. Jacob-Mosier, R.G. Lawton,R.R. Neubig. " A new thiol specific photoactivatable crosslinking regent. Conjugation of an alpha 2-adrenergic receptor peptide to G-protein". Peptides, 1994, 15, 829-834.
J.M. Taylor, G.G. Jacob-Mosier, R.G. Lawton, A.E. Remmers, R. Neubig. "Binding of an alpha 2-adrenergic receptor third intercellular loop peptide to G beta and the amino terminus of G alpha ". J. Biol. Chem.1994, 45, 27618-27624.
Yaun-Shek Chen, Jeff W. Kampf and Richard G. Lawton. "Aromatic Stacking in Folded Architectures through Hydrogen Bonding." Tetrahedron Lett. 1997, 38, 5781-5184.
S.J. Brocchini, R.G. Lawton. "Titanium Chelation in Regioselective Michael Additions to Conjugated Dienones and Trienones". Tetrahedron Lett. 1997, 38, 6319-6323.
Y.S. Chen, J.W. Kampf, .G.Lawton. "Intramolecular Carboxylate Capture of an Intermediate in Aromatic Electrophilic Substitution. The 8,9,10,11-tetrahydro-7.11-methano-7H-cycloocta[de]naphthalene-9-endo-carboxylic acid System". Tetrahedron Lett. 1997, 38, 6831-6834.