Peptides to overcome inhibition of nerve growth

Details Peptides to overcome inhibition of nerve growth Peptides to overcome inhibition of nerve growth

1995-04-05

1996-08-06

Draper, Garnette D.

Chemistry: natural resins or derivatives; peptides or proteins;

Peptides of 3 to 100 amino acid residues

8 to 10 amino acid residues in defined sequence

A61K 3800, A61K 3804, C07K 706

Patent

active

055434983

ABSTRACT:
Inhibition of nerve growth normally helps to prevent aberrant pathway or target selection, but also prevents needed regeneration in the mammalian central nervous system. The responsible inhibitory ligands are unknown, but pertussis toxin-sensitive G proteins, which are enriched in growth cones, appear to be involved in causing the responding growth cones to collapse. GAP-43 is an intracellular protein that can amplify the response to the stimulation of G protein-coupled receptors. We have attempted to modify the sensitivity of nerves to inhibitory signals by the use of GAP-43 peptides. The peptide corresponding to the native amino terminus sequence stimulates G.sub.o and enhances the growth cone collapse induced by inhibitory ligands. Modification of two critical cysteines generates peptides which inhibit G.sub.o and which markedly reduce the degree of inhibitor-mediated growth cone collapse.

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