H-1 NMR structural characterization of a nonmitogenic, vasodilatory, ischemia-protector and neuromodulatory acidic fibroblast growth factor

A shortened genetically engineered form of acidic fibroblast growth factor (aFGF), that includes amino acids 28-154 of the full-length sequence (154 r esidues) plus Met in substitution of Leu27, does not induce cell division e ven though it is recognized by the cell membrane receptor, triggers the ear ly mitogenic events, and retains the neuromodulatory, vasoactive, and cardi o- and neuroprotective properties of the native full-length molecule. Taken together, these properties make this truncated aFGF a promising compound i n the treatment of a wide assortment of neurological and cardiovascular pat hologies where aFGF mitogenic activity is dispensable. Differences in biolo gical activities between the shortened aFGF and the wild-type form have bee n attributed to lack of stability, and to the specific amino acid sequence missing at the N-terminus, Here we show that this shortened aFGF form has a three-dimensional structure even more stable than the wild-type protein at the mitogenic assay conditions; that this structure is similar to that of the wild type except at site 1 of interaction with the cell membrane recept or; that its lack of mitogenic activity cannot be attributed to the specifi c missing sequence; and that the vasodilatory activity of aFGF seems impair ed by alterations of the three-dimensional structure of site 2 of interacti on with the cell membrane receptor.