Compositions comprising Sel1-derived peptides and methods of treatment/prevention of excess oxalate levels and associated conditions/diseases therewith
Provided herein are compositions comprising Sel1-derived peptides thereof, and method of use thereof for the treatment/prevention excess oxalate levels and conditions and diseases related thereto. In particular, peptides comprise Sel-like repeat (SLR) domains and/or tetratricopeptide (TPR) domains and may be linked together or with other peptides or polypeptides to treat/prevent diseases/conditions related to excess oxalate levels, such as hyperoxaluria and/or hyperoxalemia.
1. A method of stimulating oxalate transport comprising administering to a subject a pharmaceutical composition comprising a suppressor-enhancer of lin 1 (Sel1)-derived peptide, wherein the Sel1-derived peptide comprises (i) the amino acid sequence of SEQ ID NO: 52 or 53 or (ii) the amino acid sequence that is at least 90% identical to SEQ ID NO: 12 or 13, and wherein the Sel1-derived peptide is no more than about 50 amino acids in length.
2. The method of claim 1 , wherein the administration is rectal administration, oral administration, or injection.
3. The method of claim 1 , wherein the subject suffers from or is at risk for hyperoxaluria and/or hyperoxalemia.
4. The method of claim 1 , wherein the subject's risk of calcium oxalate kidney stones, nephrocalcinosis, oxalate nephropathy, end stage renal disease, chronic kidney disease, and/or systemic oxalosis is lowered by the administration.
5. The method of claim 1 , wherein the Sel1-derived peptide comprises the amino acid sequence that is at least 90% identical to SEQ ID NO: 12 or 13.
6. The method of claim 1 , wherein the Sel1-derived peptide comprises the amino acid sequence of SEQ ID NO: 52 or 53.
7. The method of claim 1 , wherein the composition comprises 2 or more of the Sel1-derived peptides.
8. The method of claim 7 , wherein the two or more Sel1-derived peptides are fused directly or indirectly to each other.
9. The method of claim 7 , wherein the two or more Sel1-derived peptides are not fused to each other.
10. The method of claim 1 , wherein:
(i) the Sel1-derived peptide comprises one or more D enantiomers,
(ii) the Sel1-derived peptide comprises one or more unnatural amino acids,
(iii) the Sel1-derived peptide comprises one or more amino acid analogs, and/or
(iv) the Sel1-derived peptide comprises one or more peptoid amino acids.
11. The method of claim 1 , wherein the Sel1-derived peptide comprises a modification selected from the group consisting of phosphorylation, glycosylation, ubiquitination, S-nitrosylation, methylation, N-acetylation, C-terminal amidation, cyclization, substitution of natural L-amino acids with non-natural D-amino acids, lipidation, lipoylation, deimination, eliminylation, disulfide bridging, isoaspartate formation, racemization, glycation, carbamylation, carbonylation, isopeptide bond formation, sulfation, succinylation, S-sulfonylation, S-sulfinylation, S-sulfenylation, S-glutathionylation, pyroglutamate formation, propionylation, adenylylation, nucleotide addition, iodination, hydroxylation, malonylation, butyrylation, amidation, alkylation, acylation, biotinylation, carbamylation, oxidation, and pegylation.
12. The method of claim 1 , wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier.
13. The method of claim 12 , wherein the pharmaceutical composition further comprises one or more additional therapeutic agents.