In vitro inhibition of the actions of basic FGF by a novel 16 amino acid peptide

A composite procedure involving molecular modelling and a property-pattern algorithm, the Resonant Recognition Model (RRM), has been applied to structure-function studies with basic fibroblast growth factor (bFGF). Propertypattern characteristics for biological activity and receptor recognition for a group of FGF-related proteins were de fined and then used to aid the design of a set of peptides which can act as bFGF antagonists. Molecular modelling techniques were then employed to identify the peptide within this set with the greatest conformational similarity to the putative receptor domain of bFGF. This 16 amino acid residue peptide (16mer), which exhibits no sequence homology to bFGF, antagonised the stimulatory effect of bFGF on fibroblast [3H]thymidine incorporation and cell proliferation, but exerted no effect itself in thesein vitro bioassays.

[1]  G. Peters,et al.  Potential oncogene product related to growth factors , 1987, Nature.

[2]  J. Folkman,et al.  TUMOR DORMANCY IN VIVO BY PREVENTION OF NEOVASCULARIZATION , 1972, The Journal of experimental medicine.

[3]  H. Burger,et al.  Direct inhibition of rat granulosa cell inhibin production by epidermal growth factor in vitro , 1987, Molecular and Cellular Endocrinology.

[4]  P. Bohlen,et al.  Corpus luteum angiogenic factor is related to fibroblast growth factor. , 1985, Endocrinology.

[5]  I Cosic,et al.  Prediction of "hot spots" in interleukin-2 based on informational spectrum characteristics of growth-regulating factors. Comparison with experimental data. , 1989, Biochimie.

[6]  D. Gospodarowicz.  Fibroblast and epidermal growth factors: their uses in vivo and in vitro in studies on cell functions and cell transplantation , 1979, Molecular and Cellular Biochemistry.

[7]  D. Rifkin,et al.  Endothelial cell-derived heparan sulfate binds basic fibroblast growth factor and protects it from proteolytic degradation , 1988, The Journal of cell biology.

[8]  D. Gospodarowicz.  Purification of a fibroblast growth factor from bovine pituitary. , 1975, The Journal of biological chemistry.

[9]  M Karplus,et al.  Dynamics of proteins: elements and function. , 1983, Annual review of biochemistry.

[10]  A. Moses,et al.  Adenosine 3',5'-monophosphate mediates both the mitogenic effect of thyrotropin and its ability to amplify the response to insulin-like growth factor I in FRTL5 cells. , 1988, Endocrinology.

[11]  D. Rees,et al.  Three-dimensional structures of acidic and basic fibroblast growth factors. , 1993, Science.

[12]  M T Hearn,et al.  Resonant recognition model and protein topography. Model studies with myoglobin, hemoglobin and lysozyme. , 1991, European journal of biochemistry.

[13]  T. Davies.  Positive regulation of the guinea pig thyrotropin receptor. , 1985, Endocrinology.

[14]  M. Klagsbrun.  Mediators of angiogenesis: the biological significance of basic fibroblast growth factor (bFGF)-heparin and heparan sulfate interactions. , 1992, Seminars in cancer biology.

[15]  H. Hanafusa,et al.  Characterization of the murine BEK fibroblast growth factor (FGF) receptor: activation by three members of the FGF family and requirement for heparin. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[16]  T. Yamamuro,et al.  Transforming growth factor β modulates proliferation of osteoblastic cells: Relation to its effect on receptor levels for epidermal growth factor , 1989 .

[17]  Robert Langer,et al.  Angiogenesis, Key principles, Science, Technology, Medicine , 1992 .

[18]  C. K. Yuen,et al.  Theory and Application of Digital Signal Processing , 1978, IEEE Transactions on Systems, Man, and Cybernetics.

[19]  D. Gospodarowicz,et al.  Mitogenic effect of fibroblast growth factor on early passage cultures of human and murine fibroblasts , 1975, The Journal of cell biology.

[20]  A. Warner.  Gap junctions in development--a perspective. , 1992, Seminars in cell biology.

[21]  Jeffrey D. Esko,et al.  Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor , 1991, Cell.

[22]  D. Moscatelli,et al.  High and low affinity binding sites for basic fibroblast growth factor on cultured cells: Absence of a role for low affinity binding in the stimulation of plasminogen activator production by bovine capillary endothelial cells , 1987, Journal of cellular physiology.

[23]  M T Hearn,et al.  Studies on protein-DNA interactions using the resonant recognition model. Application to repressors and transforming proteins. , 1992, European journal of biochemistry.

[24]  R Guillemin,et al.  Receptor- and heparin-binding domains of basic fibroblast growth factor. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[25]  R. Hintz,et al.  Direct Evidence that the Insulin Receptor Mediates a Mitogenic Response in Cultured Human Fibroblasts , 1989, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[26]  D. Rifkin,et al.  Processing, secretion, and biological properties of a novel growth factor of the fibroblast growth factor family with oncogenic potential , 1988, Molecular and cellular biology.

[27]  G. Risbridger,et al.  Effect of cryptorchidism on steroidogenic and mitogenic activities in rat testicular interstitial fluid. , 1987, Journal of reproduction and fertility.

[28]  J. Folkman,et al.  Relation of vascular proliferation to tumor growth. , 1976, International review of experimental pathology.

[29]  D. Rifkin,et al.  Autocrine activities of basic fibroblast growth factor: regulation of endothelial cell movement, plasminogen activator synthesis, and DNA synthesis , 1988, The Journal of cell biology.

[30]  M. Klagsbrun,et al.  Purification and characterization of heparin-binding endothelial cell growth factors. , 1986, The Journal of biological chemistry.

[31]  Angiogenesis factors. , 2001, Internal medicine.

[32]  J. Folkman.  Angiogenesis--retrospect and outlook. , 1992, EXS.

[33]  D. Gospodarowicz,et al.  Heparin protects basic and acidic FGF from inactivation , 1986, Journal of cellular physiology.

[34]  L. Orci,et al.  Basic fibroblast growth factor induces angiogenesis in vitro. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[35]  R. Mitchell,et al.  Bovine granulosa cells produce basic fibroblast growth factor. , 1987, Endocrinology.

[36]  P. Morméde,et al.  Immunoreactive fibroblast growth factor in cells of peritoneal exudate suggests its identity with macrophage-derived growth factor. , 1985, Biochemical and biophysical research communications.

[37]  M. Ittmann,et al.  An oncogene isolated by transfection of Kaposi's sarcoma DNA encodes a growth factor that is a member of the FGF family , 1987, Cell.

[38]  J. Slack,et al.  Mesoderm induction in early Xenopus embryos by heparin-binding growth factors , 1987, Nature.

[39]  V. Veljković,et al.  Simple General-Model Pseudopotential , 1972 .