Method and composition for enhancing transport across biological membranes
First Claim
1. A conjugate for administration, to a mammalian subject, of an antimicrobial agent whose efficacy in non-conjugated form is limited by its solubility in aqueous liquid or its inability to cross biological membranes to manifest biological activity, said conjugate comprises a transport peptide covalently attached by a linker to the antimicrobial agent, said linker being cleaved in vivo to release the antimicrobial agent from the linker and the transport peptide, wherein the attached transport peptide:
- (a) consists of from 6 to 25 amino acid residues, at least 50% of which contain a guanidino sidechain having the structure or an amidino sidechain having the structure wherein n is 2, 3, 4 or 5;
(b) contains at least 6 contiguous amino acid residues containing said guanidino or amidino sidechain; and
(c) increases the delivery of the antimicrobial agent across a biological membrane relative to the delivery of the antimicrobial agent in non-conjugated form.
1 Assignment
0 Petitions
Accused Products
Abstract
Methods and compositions for transporting drugs and macromolecules across biological membranes are disclosed. In one embodiment, the invention includes a method for enhancing transport of a selected compound across a biological membrane, wherein a biological membrane is contacted with a conjugate containing a biologically active agent that is covalently attached to a transport polymer. In one embodiment, the polymer consists of from 6 to 25 subunits, at least 50% of which contain a guanidino or amidino sidechain moiety. The polymer is effective to impart to the attached agent a rate of trans-membrane transport across a biological membrane that is greater than the rate of trans-membrane transport of the agent in non-conjugated form.
-
Citations
18 Claims
-
1. A conjugate for administration, to a mammalian subject, of an antimicrobial agent whose efficacy in non-conjugated form is limited by its solubility in aqueous liquid or its inability to cross biological membranes to manifest biological activity, said conjugate comprises a transport peptide covalently attached by a linker to the antimicrobial agent, said linker being cleaved in vivo to release the antimicrobial agent from the linker and the transport peptide, wherein the attached transport peptide:
-
(a) consists of from 6 to 25 amino acid residues, at least 50% of which contain a guanidino sidechain having the structure or an amidino sidechain having the structure wherein n is 2, 3, 4 or 5; (b) contains at least 6 contiguous amino acid residues containing said guanidino or amidino sidechain; and
(c) increases the delivery of the antimicrobial agent across a biological membrane relative to the delivery of the antimicrobial agent in non-conjugated form. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18)
-
Specification