Parathyroid hormone analogs, compositions and uses thereof
AssigneesThe General Hospital Corporation, Sloan-Kettering Institute for Cancer Research
InventorsSamuel J. Danishefsky, Shiying Shang, Zhongping Tan, Suwei Dong, Jianfeng Li, Thomas Gardella
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Abstract
The present invention provides parathyroid hormone and/or parathyroid hormone-related protein analogs, compositions thereof and methods thereto.
Claims31
A parathyroid hormone peptide 1-84 amino acids in length having an amino acid sequence ≧80% identical to SEQ ID NO:
- 2, wherein the parathyroid hormone peptide includes a non-natural amino acid at one or more positions corresponding to residues X1, X7, X8, X16, X18, X21, X22, X26, X35, X36, X39, X40, X41, X42, X43, X45, X46, X47, X48, X52, X56, X58, X59, X60, X61, X62, X63, X64, X70, X74, X76, X79, X81 or X83.
A parathyroid hormone peptide 1-37 amino acids in length having an amino acid sequence ≧80% identical to SEQ ID NO:
- 15, wherein the parathyroid hormone peptide includes a norleucine and/or methoxinine residue at a position corresponding to residue 8, residue 18 and combinations thereof.
A parathyroid hormone peptide having an amino acid sequence which includes an element ≧80% identical to SEQ ID NO:
- 14, wherein the parathyroid hormone peptide includes a norleucine and/or methoxinine residue at a position corresponding to residue 8, residue 18 and combinations thereof.
A parathyroid hormone-related peptide 1-141 amino acids in length having an amino acid sequence ≧80% identical to SEQ ID NO:
- 8.
A method of preparing a biologically active hormone or glycopeptide comprising at least one native chemical ligation coupling at an amino acid residue other than cysteine or methionine.
A native chemical ligation fragment selected from the group consisting of:
- I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVIII, XXIX, XXX, XXXI, XXXII, XXXIII, XXXIV, XXXV, XXXVI or XXXVII.
A method of treating a disease, disorder and/or symptom associated with hypoparathyroidism comprising administering a therapeutically effective amount of a hPTH or hPTHrP peptide and/or analog.
Dependencies are inferred from the claim text.