Inhibition of cellular proliferation by peptide analogues of insulin-like growth factor 1.
The activation of the insulin-like growth factor 1 (IGF-1) receptor by its ligand plays a central role in the growth of most cell types. We have used the techniques of computational chemistry in order to design and synthesize several novel analogues of IGF-1. These analogues were able to inhibit the autophosphorylation of the IGF-1 receptor as well as the growth of several different cell types, including prostate carcinoma cells and SV40-transformed cells. Additionally, we have found that D-amino acid analogues of these peptides are apparently resistant to the proteolytic degradation that occurs in the presence of whole sera. Consequently, these analogues seem to show great potential both as probes of the structure/function activities of the IGF-1 signalling pathway and as novel clinical strategies in controlling abnormal cellular growth.
Pietrzkowski
Z
Z
Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107-5541.
Wernicke
D
D
Porcu
P
P
Jameson
B A
BA
Baserga
R
R
D016475:3T3 Cells; D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D005347:Fibroblasts; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008956:Models, Chemical; D010766:Phosphorylation; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D017526:Receptor, IGF Type 1 / Q000378:metabolism
D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1