Methylated lysine-rich lytic peptides and method of making same

Details Methylated lysine-rich lytic peptides and method of making same Methylated lysine-rich lytic peptides and method of making same

1995-04-24

1998-02-10

Scheiner, Toni R.

Chemistry: natural resins or derivatives; peptides or proteins;

Peptides of 3 to 100 amino acid residues

25 or more amino acid residues in defined sequence

514 12, C07K 500, C07K 700, C07K 1700, A61K 3800

Patent

active

057170649

ABSTRACT:
A tryptic digestion-resistant, non-naturally occurring lytic peptide comprising a sequence of amino acid residues containing mainly alanine, valine and lysine amino acid residues, wherein the .epsilon.-amino groups of the lysine residues and the .alpha.-amino group of the N-terminal amino acid are sufficiently methylated to impart enhanced tryptic, chymotryptic, and aminopeptidase digestion resistance to the peptide. The secondary conformation of the peptide is an ordered periodic structure such as an amphipathic .alpha.-helix or a .beta.-pleated sheet. The compositions of the invention are suitable for in vivo administration.
A method of making the same, to impart enhanced tryptic digestion-resistance thereto, comprising reductively alkylating the .epsilon.-amino groups of the lysine residues and the .alpha.-amino group of the N-terminal amino acid with a methyl-providing reagent in the presence of an heterocyclic amine-borane reducing agent for sufficient time and at sufficient conditions to methylate the .alpha.-and .epsilon.-amino groups to sufficient extent to confer enhanced proteolytic digestion-resistance to the peptide.

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