Peptide-mediated non-covalent delivery of active agents across the blood-brain barrier
AssigneeMayo Foundation for Medical Education and Research
InventorsGeoffry L. Curran, Gobinda Sarkar, Joseph F. Poduslo, Robert B. Jenkins, Val J. Lowe, Eric W. Mahlum
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Abstract
The peptides described herein can function as carrier peptides. These peptides can associate with (e.g., non-covalently bind) biologically active molecules or imaging agents to transport the biologically active molecules or imaging across the blood-brain barrier. In some cases, such transport may increase the effectiveness of the biological molecules or imaging agents.
Claims17
A method of transporting a biologically active molecule or imaging agent across the blood-brain barrier of a subject, the method comprising administering to the subject a complex, or a pharmaceutically acceptable salt thereof, comprising the biologically active molecule or imaging agent associated with a carrier peptide;
- wherein the carrier peptide consists of the sequence:
- Xn—[B]m
- or a pharmaceutically acceptable salt thereof, wherein:
- X is a hydrophilic amino acid;
- B is a blood-brain barrier agent of the sequence
- (SEQ ID NO:
- 29)
- L-R-X1-R-X2-X3-X4-H-L-R-X5-X6-X7-K-R-L-X8-R-D-X9,
- wherein:
- X1 is selected from the group consisting of A, L, S, and V;
- X2 is selected from the group consisting of L and M;
- X3 is selected from the group consisting of A and S;
- X4 is selected from the group consisting of N, S, and T;
- X5 is selected from the group consisting of K and N;
- X6 is selected from the group consisting of L, M, and V;
- X7 is selected from the group consisting of R and P;
- X8 is selected from the group consisting of L and M;
- and
- X9 is selected from the group consisting of A and L;
- n is an integer from 4 to 50;
- and
- m is integer from 1 to 3.
A method of treating a brain disorder in a subject, the method comprising administering to the subject a complex, or a pharmaceutically acceptable salt thereof, comprising a biologically active agent associated with a carrier peptide, wherein the carrier peptide consists of the sequence:
- Xn—[B]m
- wherein:
- X is a hydrophilic amino acid;
- B is a blood-brain barrier agent of the sequence L-R-X1-R-X2-X3-X4-H-L-R-X5-X6-X7-K-R-L-X8-R-D-X9 (SEQ ID NO:29), wherein:
- X1 is selected from the group consisting of A, L, S, and V;
- X2 is selected from the group consisting of L and M;
- X3 is selected from the group consisting of A and S;
- X4 is selected from the group consisting of N, S, and T;
- X5 is selected from the group consisting of K and N;
- X6 is selected from the group consisting of L, M, and V;
- X7 is selected from the group consisting of R and P;
- X8 is selected from the group consisting of L and M;
- and
- X9 is selected from the group consisting of A and L;
- n is an integer from 4 to 50;
- and
- m is integer from 1 to 3.
A method of imaging the central nervous system of a subject, the method comprising administering to the subject a complex, or a pharmaceutically acceptable salt thereof, comprising an imaging agent associated with a carrier peptide, wherein the carrier peptide consists of the sequence:
- Xn—[B]m
- wherein:
- X is a hydrophilic amino acid;
- B is a blood-brain barrier agent of the sequence L-R-X1-R-X2-X3-X4-H-L-R-X5-X6-X7-K-R-L-X8-R-D-X9 (SEQ ID NO:29), wherein:
- X1 is selected from the group consisting of A, L, S, and V;
- X2 is selected from the group consisting of L and M;
- X3 is selected from the group consisting of A and S;
- X4 is selected from the group consisting of N, S, and T;
- X5 is selected from the group consisting of K and N;
- X6 is selected from the group consisting of L, M, and V;
- X7 is selected from the group consisting of R and P;
- X8 is selected from the group consisting of L and M;
- and
- X9 is selected from the group consisting of A and L;
- n is an integer from 4 to 50;
- and
- m is integer from 1 to 3;
- and
- imaging the central nervous system of the subject.
Dependencies are inferred from the claim text.