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Chemokines & immunology
Chemokines play key roles in the regulation of the immune response to disease & infection. As such these proteins and their receptors have great therapeutic potential. CBV has experience in this therapeutic space & can provide expert project & portfolio review and advice.
Hunter MG, Bawden L, Brotherton D, Craig S, Cribbes S, Czaplewski LG, Dexter TM, Drummond AH, Heyworth CM, Lord BI, McCourt M, Varley PG, Wood LM, Edwards RM, Lewis PJ. BB-10010: An active variant of human macrophage inflammatory protein-1 alpha with improved pharmaceutical properties. Blood 86 (12) 4400-4408, 1995.
Czaplewski LG, McKeating J., Craven CJ, Higgins LD, Appay V, Brown A, Dudgeon T, Howard LA, Meyers T, Owen J, Palan SR, Tan P, Wilson G, Woods NR, Heyworth CM, Lord BI, Brotherton D, Christison R, Craig S, Cribbes S, Edwards RM, Evans SJ, Gilbert R, Morgan P, Randle E, Schofield N, Varley PG, Waltho JP, Hunter MG. Identification of amino acid residues critical for aggregation of human CC chemokines MIP-1alpha, MIP-1 beta, and RANTES: characterisation of active disaggregated variants. JBC 274, 16077-16084, 1999.
Buckle A-M., Craig S., Czaplewski LG. Assays for macrophage inflammatory proteins. Methods in Enzymology 287: 127-148, 1997.
Czaplewski LG., McCourt M., Hunter MG., Lord BI., Millar A., Wood LM. Engineering, biology and clinical development of hMIP-1 alpha in Chemokines in Human Disease (Hebert C., ed.) Humana Press Inc, Totowa NJ. 1998.
Trkola, A., Gordon, C., Matthews, J., Maxwell, E., Ketas, T., Czaplewski, L., Proudfoot, A.E.I., and Moore, J. The CC chemokine RANTES increases the attachment of human immunodeficiency virus type 1 to target cells via glycosaminoglycans, and also activates a signal transduction pathway that enhances viral infectivity. J. Virology 73, 6370-6379 1999.
Appay V, Brown A, Cribbes S, Randle E, Hunter MG, Czaplewski LG. Aggregation of RANTES is responsible for its inflammatory properties: Characterisation of non-aggregating, non-inflammatory RANTES mutants. JBC 274, 27505-27512 1999.
NMR structure of BB-10010 from Czaplewski et al.
Graphic prepared using PyMol.