Increasing blood-brain barrier permeability with permeabilizer peptides

A pharmaceutical composition for administration to an animal to increase the permeability of the blood-brain barrier to a molecule, comprising:

• a) an effective amount of a peptide having the amino acid sequence of R-arginine-proline-hydroxyproline-glycine-thienylalanine-serine-proline-(4 -Me-tyrosine).psi.(CH.sub.2 NH)arginine-OH (SEQ ID No.:1) or a conformational analogue thereof which is said peptide with at least one of the following modifications:
• i) the arginine closest to R is replaced by an amino acid analogue containing a guanidino side chain;
• ii) the proline closest to R is replaced by hydroxyproline, dehydroproline or N-methylalanine;
• iii) the hydroxyproline is replaced by proline, dehydroproline, alanine or N-methylalanine;
• iv) the thienylalanine is replaced by another aromatic amino acid or a hydrophobic aliphatic amino acid;
• v) the serine is replaced by glycine or alanine;
• vi) the proline closest to the C-terminal is replaced by hydroxyproline, dehydroproline or N-methylalanine;
• and
• vii) the C-terminal arginine is replaced by an amino acid analogue containing a guanidino side chain;
• wherein R is selected from the group consisting of acetyl, arginine, acetyl arginine, propyl arginine, benzyl arginine, arginine--arginine, methionine-arginine, lysine, lysine--lysine and methionine-lysine;
• and
• b) a pharmaceutically acceptable carrier.

A method for increasing the permeability of the blood-brain barrier of a host to carboplatin present in the bloodstream of the host comprising the intravascular administration of an effective amount of a blood-brain barrier permeabilizer comprising a peptide with the amino acid sequence of ›H!R-arginine-proline-hydroxyproline-glycine-thienylalanine-serine-proline -(4-Me-tyrosine).psi.(CH.sub.2 NH)arginine-OH (SEQ ID NO:

• 1) or a conformational analogue thereof which is said peptide with at least one of the following modifications:
• a) the arginine closest to R is replaced by an amino acid analogue containing a guanidino side chain;
• b) the proline closest to R is replaced by hydroxyproline, dehydroproline or N-methylalanine;
• c) the hydroxyproline is replaced by prolinee dehydroproline,ko alanine or N-methylalanine;
• d) the thienylalanine is replaced by another aromatic amino acid or a hydrophobic aliphatic amino acid;
• e) the serine is replaced by glycine or alanine;
• f) the proline closest to the C-terminal is replaced by hydroxyproline, dehydroproline or N-methylalanine;
• and
• g) the C-terminal arginine is replaced by an amino acid analogue containing a guanidino side chain;
• wherein R is selected from the group consisting of H, acetyl, arginine, acetyl arginine, propyl arginine, benzyl arginine, arginine--arginine, methionine-arginine, lysine, lysine--lysine and methionine-lysine.