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). Property-pattern characteristics for biological activity and receptor recognition for a group of FGF-related proteins were defined 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 these in vitro bioassays.
Cosic
I
I
Department of Biochemistry, Monash University, Clayton, Victoria, Australia.
Drummond
A E
AE
Underwood
J R
JR
Hearn
M T
MT
D000465:Algorithms; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D017076:Computer-Aided Design; D016222:Fibroblast Growth Factor 2 / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000494:pharmacology*; D005583:Fourier Analysis; D006801:Humans; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*
D000596:Amino Acids; D010455:Peptides; D016222:Fibroblast Growth Factor 2