Methods and compositions related to peptides and proteins with c-terminal elements
AssigneeSanford Burnham Prebys Medical Discovery 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.
Claims20
A method of forming an activatable CendR element, the method comprising (a) selecting an amino acid sequence for internalization into a cell, tissue penetration, or both, wherein the amino acid sequence comprises a CendR element comprising a terminal carboxyl group, (b) causing a blocking group to be covalently coupled to the terminal carboxyl group of the CendR element, wherein a bond coupling the blocking group and the CendR element is cleavable, wherein the blocking group covalently coupled to the CendR element reduces or prevents internalization into a cell, tissue penetration, or both, wherein the activatable CendR element comprises the selected amino acid sequence and the blocking group, wherein cleavage of the activatable CendR element exposes the terminal carboxyl group of the CendR element, wherein the amino acid sequence is circular, and wherein the CendR element comprises the sequence KLAK (amino acids 11-14 of SEQ ID NO:5), KPAR (amino acids 4-7 of SEQ ID NO:
- 114), KPER (amino acids 4-7 of SEQ ID NO:90), KPLR (amino acids 4-7 of SEQ ID NO:
- 63), KPRR (amino acids 5-8 of SEQ ID NO:
- 126), KQAR (amino acids 4-7 of SEQ ID NO:
- 64), KRDR (amino acids 3-6 of SEQ ID NO:89), KRER (amino acids 4-7 of SEQ ID NO:91), KTAR (amino acids 3-6 of SEQ ID NO:56), RGDK (amino acids 2-5 of SEQ ID NO:4), RPAK (amino acids 4-7 of SEQ ID NO:
- 112), or RTPK (amino acids 4-7 of SEQ ID NO:84).
An activatable CendR element made by a method comprising (a) selecting an amino acid sequence for internalization into a cell, tissue penetration, or both, wherein the amino acid sequence comprises a CendR element comprising a terminal carboxyl group, (b) causing a blocking group to be covalently coupled to the to the terminal carboxyl group of the CendR element, wherein a bond coupling the blocking group and the CendR element is cleavable, wherein the blocking group covalently coupled to the CendR element reduces or prevents internalization into a cell, tissue penetration, or both, wherein the activatable CendR element comprises the selected amino acid sequence and the blocking group, wherein cleavage of the activatable CendR element exposes the terminal carboxyl group of the CendR element, and wherein the amino acid sequence is circular, and wherein the CendR element comprises the sequence KLAK (amino acids 11-14 of SEQ ID NO:5), KPAR (amino acids 4-7 of SEQ ID NO:
- 114), KPER (amino acids 4-7 of SEQ ID NO:90), KPLR (amino acids 4-7 of SEQ ID NO:
- 63), KPRR (amino acids 5-8 of SEQ ID NO:
- 126), KQAR (amino acids 4-7 of SEQ ID NO:
- 64), KRDR (amino acids 3-6 of SEQ ID NO:89), KRER (amino acids 4-7 of SEQ ID NO:91), KTAR (amino acids 3-6 of SEQ ID NO:56), RGDK (amino acids 2-5 of SEQ ID NO:4), RPAK (amino acids 4-7 of SEQ ID NO:112), or RTPK (amino acids 4-7 of SEQ ID NO:84).
Dependencies are inferred from the claim text.