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Updated: Aug 5, 2026
A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors
Published on: March 15, 2016
1H NMR structural characterization of a nonmitogenic, vasodilatory, ischemia-protector and neuromodulatory acidic
R M Lozano1, A Pineda-Lucena, C Gonzalez
1Centro de Investigaciones Biológicas (CSIC), Velázquez 144, 28006 Madrid, Spain.
Abstract:
A shortened genetically engineered form of acidic fibroblast growth factor (aFGF), that includes amino acids 28-154 of the full-length sequence (154 residues) plus Met in substitution of Leu27, does not induce cell division even though it is recognized by the cell membrane receptor, triggers the early mitogenic events, and retains the neuromodulatory, vasoactive, and cardio- and neuroprotective properties of the native full-length molecule. Taken together, these properties make this truncated aFGF a promising compound in the treatment of a wide assortment of neurological and cardiovascular pathologies where aFGF mitogenic activity is dispensable. Differences in biological activities between the shortened aFGF and the wild-type form have been 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 receptor; that its lack of mitogenic activity cannot be attributed to the specific missing sequence; and that the vasodilatory activity of aFGF seems impaired by alterations of the three-dimensional structure of site 2 of interaction with the cell membrane receptor.
Insights
A shortened acidic fibroblast growth factor (aFGF) retains therapeutic properties but lacks cell division induction. Structural analysis reveals altered receptor interaction sites explain its reduced mitogenic and vasodilatory activities.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Acidic fibroblast growth factor (aFGF) is a potent signaling molecule with therapeutic potential.
- A truncated aFGF variant (amino acids 28-154) retains non-mitogenic functions but lacks cell division induction.
- Previous hypotheses attributed functional differences to instability or N-terminal sequence absence.
Purpose of the Study:
- To investigate the structural and functional basis for the lack of mitogenic activity in a shortened aFGF variant.
- To compare the stability and receptor interaction of the truncated aFGF with the wild-type form.
- To elucidate the mechanisms underlying the altered biological activities of the engineered aFGF.
Main Methods:
- Structural analysis of the shortened aFGF.
- Comparison of three-dimensional structures between wild-type and truncated aFGF.
- Assessment of receptor interaction sites (Site 1 and Site 2).
- Evaluation of mitogenic and vasodilatory activities.
Main Results:
- The shortened aFGF exhibits enhanced structural stability under assay conditions compared to wild-type aFGF.
- Structural similarity exists between the forms, except at the cell membrane receptor interaction Site 1.
- The absence of the N-terminal sequence does not account for the lack of mitogenic activity.
- Alterations in the three-dimensional structure of Site 2 impair the vasodilatory activity of the shortened aFGF.
Conclusions:
- The engineered shortened aFGF is structurally stable and retains key therapeutic properties, making it suitable for conditions where proliferation is undesirable.
- The lack of mitogenic activity is not due to instability or missing sequence but rather specific structural changes affecting receptor interactions.
- Altered structural configuration at Site 2 of receptor interaction significantly impacts the vasodilatory function of the truncated aFGF.
