Methods and compositions using peptides and proteins with C-terminal elements
AssigneeSanford-Burnham Medical Research Institute
InventorsErkki Ruoslahti, Tambet Teesalu, Kazuki Sugahara
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Abstract
Disclosed are compositions and methods useful for targeting and internalizing molecules into cells of interest and for penetration by molecules of tissues of interest. The compositions and methods are based on peptide sequences that are selectively internalized by a cell, penetrate tissue, or both. The disclosed internalization and tissue penetration is useful for delivering therapeutic and detectable agents to cells and tissues of interest.
Claims198
A composition comprising a CendR element and a co-composition,
- wherein the CendR element and the co-composition are not directly or indirectly covalently coupled with each other, wherein there is no direct non-covalent association between the CendR element and the co-composition,
- wherein the CendR element is comprised in an amino acid sequence and is an activatable CendR element,
- wherein the CendR element binds to neuropilin-1, wherein internalization of the CendR element into cells is dependent on neuropilin-1, and
- wherein cleavage of the activatable CendR element exposes the terminal carboxyl group of the CendR element.
A composition comprising a CendR element and a co-composition, wherein the CendR element and the co-composition are indirectly non-covalently associated with each other, the CendR element and the co-composition are not covalently coupled with each other, and the CendR element and the co-composition are not directly non-covalently associated with each other, and wherein the composition does not include VEGF.
A composition comprising a CendR element and a co-composition,
- wherein the CendR element and the co-composition are not directly or indirectly covalently coupled with each other,
- wherein the CendR element is comprised in an amino acid sequence, wherein the amino acid sequence is comprised in a protein or peptide, wherein the CendR element is at the C-terminal end of the protein or peptide or is an activatable CendR element, wherein the CendR element either:
- (i) is at the C-terminal end of the amino acid sequence, and has an exposed C-terminal carboxyl group, wherein the CendR element has the sequence X1X2X3X4, wherein X1 can be R or K, X4 can be R, K or KG, and wherein X2 and X3 can each be independently any amino acid and the composition does not include VEGF;
- or
- (ii) is an activatable CendR element,
- wherein the CendR element does not include RRLR (SEQ ID NO:248), RRRR (SEQ ID NO:249), RRER (SEQ ID NO:243), KRSR (SEQ ID NO:211), KWKK (SEQ ID NO:245), RRLK (SEQ ID NO:246), or KLRK (SEQ ID NO:247), and
- wherein the CendR element binds to neuropilin-1.
A composition comprising a CendR element and a co-composition,
- wherein the CendR element and the co-composition are not directly or indirectly covalently coupled with each other, wherein there is no direct non-covalent association between the CendR element and the co-composition,
- wherein the CendR element is comprised in an amino acid sequence, is at the C-terminal end of the amino acid sequence, and has an exposed C-terminal carboxyl group, wherein the CendR element has the sequence X1X2X3X4, wherein X1 can be R or K, X4 can be R, K or KG, and wherein X, and X3 can each be independently any amino acid,
- wherein the CendR element does not include RRLR (SEQ ID NO:248), RRRR (SEQ ID NO:249), RRER (SEQ ID NO:243), KRSR (SEQ ID NO:244), KWKK (SEQ ID NO:245), RRLK (SEQ ID NO:246), or KLRK (SEQ ID NO:247),
- wherein the composition does not include VEGF, wherein the CendR element binds to neuropilin-1, and wherein internalization of the CendR element into cells is dependent on neuropilin-1.
Dependencies are inferred from the claim text.