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. 1992 Sep 1;89(17):8313–8316. doi: 10.1073/pnas.89.17.8313

Tetrapeptide inhibitors of protein farnesyltransferase: amino-terminal substitution in phenylalanine-containing tetrapeptides restores farnesylation.

M S Brown 1, J L Goldstein 1, K J Paris 1, J P Burnier 1, J C Marsters Jr 1
PMCID: PMC49908  PMID: 1518863

Abstract

Protein farnesyltransferase from rat brain transfers farnesyl residues to cysteine residues in tetrapeptides that conform to the sequence CA1A2X, where C is cysteine, A1 and A2 are aliphatic amino acids, and X is methionine or serine. When the A2 residue is aromatic [e.g., phenylalanine as in Cys-Val-Phe-Met (CVFM)], the tetrapeptide continues to bind to the enzyme, but it can no longer accept a farnesyl group, and it becomes a pure inhibitor. The current studies show that this resistance to farnesylation also requires a positive charge on the cysteine amino group. Derivatization of this group with acetyl, octanoyl, or cholic acid residues or extension of the peptide with an additional amino acid restores the ability of phenylalanine-containing peptides to accept a farnesyl residue. The same result was obtained when the amino group of cysteine was deleted (mercaptopropionyl-VFM). These data suggest that the positive change on the cysteine amino group acts in concert with an aromatic residue in the A2 position to render peptides resistant to farnesylation by the rat brain enzyme.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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