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Inhibition of Cellular Proliferation by Peptide Analogues of Insulin-like Growth Factor 1¹

Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107-5541

² To whom requests for reprints should be addressed, at Jefferson Cancer Institute, Thomas Jefferson University, Bluemle Life Sciences Building, Room 624 A, 233 S. 10th Street, Philadelphia, PA 19107-5541.

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.

¹ This work was supported by Grant GM42383 from the NIH.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 7/23/92. Accepted 9/23/92.

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