Guanylin cyclase C compound of the inventions are disclosed. Conjugated compounds comprising guanylin cyclase C compound of the inventions conjugated to detectable or therapeutic moieties are disclosed. Methods of detecting, imaging and treating cancer and treating diarrhea are disclosed.
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1. A purified compound having a structure according to formula (I) R1-R2-R3-R4-R5-R6-R7-R8-R9 (I) wherein: R1 is absent, or a combination of 1-50 natural amino acids, 1-50 blocked amino acids, 1-50 synthetic amino acids, 1-50 derivatized amino acids; 1-50 amino acid mimetics, a 1-50 alkyls, one or
1. A purified compound having a structure according to formula (I) R1-R2-R3-R4-R5-R6-R7-R8-R9 (I) wherein: R1 is absent, or a combination of 1-50 natural amino acids, 1-50 blocked amino acids, 1-50 synthetic amino acids, 1-50 derivatized amino acids; 1-50 amino acid mimetics, a 1-50 alkyls, one or more 1-50 substituted alkyls, one or more 1-50 aryls, one or more 1-50 substituted aryls, one or more 1-50 alkylaryls, one or more 1-50 substituted alkylaryls or combinations thereof;R2 is a natural, blocked, or derivatized cysteine, wherein R2 crosslinks with R6;R3 is a natural, blocked, or derivatized cysteine, wherein R3 crosslinks with R8;R4 is one or two natural, blocked, or derivatized glutamic acid or leucine wherein R4 forms a 310-helix turn group linking R3 to R5;R5 is a natural leucine, blocked leucine, derivatized leucine, natural isoleucine, blocked isoleucine, or derivatized isoleucine;R6 is a natural, blocked, or derivatized cysteine, wherein R6 crosslinks with R2;R7 is NPA, wherein R7 forms a beta turn group linking R6 to R8,R8 is a natural, blocked, or derivatized cysteine, wherein R8 crosslinks with R3;R9 is absent, or a combination of 1-50 natural amino acids, 1-50 blocked amino acids, 1-50 synthetic amino acids, 1-50 derivatized amino acids; 1-50 amino acid mimetics, a 1-50 alkyls, one or more 1-50 substituted alkyls, one or more 1-50 aryls, one or more 1-50 substituted aryls, one or more 1-50 alkylaryls, one or more 1-50 substituted alkylaryls or combinations thereof that does not crosslink to R5. 2. The compound of claim 1 wherein said compound is a conjugated compound having a compound of formula (I) conjugated to an active moiety selected from the group consisting of: a radionuclide, an enzyme, a fluorescent label, a metal chelating group, a chemiluminescent label, a bioluminescent label, a chemotherapeutic, a toxin, an inactive prodrug, a radiosensitizing agent, a photodynamic agent, a nucleic acid molecule or combinations thereof. 3. The compound of claim 1 wherein said compound is a conjugated compound having a compound of formula (I) conjugated to an active moiety selected from the group consisting of: 43K, 52Fe, 57Co, 67Cu, 67Ga, 68Ga, 77Br, 81Rb/81MKr, 87MSr, 99MTc, 111In, 113MIn, 123I, 127Cs, 129Cs, 131I, 132I, 197Hg, 203Pb, 206Bi, 47Sc, 90Y, 109Pd, 123I, 125I, 131I, 186Re, 188Re, 199Au, 211At, 212Pb and 212Bi, 32P, 33P, 71Ge, 77As, 103Pb, 105Rh, 111Ag, 119Sb, 121Sn, 131Cs, 143Pr, 161Tb, 177Lu, 191Os, 193Mpt, 197Hg; a beta negative emitter, an auger emitters; malate dehydrogenase, staphylococcal nuclease, delta-5-steroid isomerase, yeast alcohol dehydrogenase, alpha-glycerophosphate dehydrogenase, triose phosphate isomerase, horseradish peroxidase, alkaline phosphatase, asparaginase, glucose oxidase, beta-galactosidase, ribonuclease, urease, catalase, glucose-6-phosphate dehydrogenase, glucoamylase and acetylcholinesterase, fluorescein isothiocyanate, rhodamine, phycoerythrin, phycocyanin, allophycocyanin, o-phthaldehyde and fluorescamine; fluorescence-emitting metals; diethylenetriaminepentaacetic acid (DTPA), ethylenediamine-tetraacetic acid (EDTA), luminol, isoluminol, theromatic acridinium ester, imidazole, acridinium salt and oxalate ester; luciferin, luciferase aequorin, methotrexate (amethopterin), doxorubicin (adrimycin), daunorubicin, cytosinarabinoside, etoposide, 5-4 fluorouracil, melphalan, chlorambucil, cyclophosphamide, cis-platinum, vindesine, mitomycin, bleomycin, purothionin, macromomycin, 1,4-benzoquinone derivatives, trenimon, ricin, ricin A chain, Pseudomonas exotoxin (PE), diphtheria toxin (DT), Clostridium perfringens phospholipase C (PLC), bovine pancreatic ribonuclease (BPR), pokeweed antiviral protein (PAP), abrin, abrin A chain (abrin toxin), cobra venom factor (CVF), gelonin (GEL), saporin (SAP), modeccin, viscumin and volkensin; etoposidephosphate, nitroimidazoles, metronidazole, misonidazole; 43K, 52Fe, 57Co, 67Cu, 67Ga, 68Ga, 77Br, 81Rb/81MKr, 87MSr, 99MTc, 111In, 113MIn, 123I, 127Cs, 129Cs, 131I, 132I, 197Hg, 203Pb, 206206Bi, 47Sc, 90Y, 109Pd, 123I, 125I, 131I, 186Re, 188Re, 199Au, 211At, 212Pb and 212Bi, 32P, 33P, 71Ge, 77As, 103Pb, 105Rh, 111Ag, 119Sb, 121Sn, 131Cs, 143Pr, 161Tb, 177Lu, 191Os, 193Mpt, 197Hg, 47Sc, and 206206Bi, fluorophore hematoporphyrin derivative (HPD), porfimer sodium, BPD verteporfin and tetramethylrotamine. 4. A compounds of any one of claims 1-3 wherein R1 is Y, NTFY (SEQ ID NO:12), SSSNY (SEQ ID NO:9), SSDWDY (SEQ ID NO:10), ID, PN, or QE;R2 is C cross linked to C at R6;R3 is a C crosslinked to C at R8;R4 is E-L, or E-NmethylLeu;R5 is L,-or NmethylLeu;R6 is C cross linked to C at R2,R7 is N-P-A;R8 is C crosslinked to C at R3; andR9 is AGA or Y. 5. A composition comprising liposomes that comprise a compound of claim 1 and an active moiety selected from the group consisting of: a radionuclide, an enzyme, a fluorescent label, a metal chelating group, a chemiluminescent label, a bioluminescent label, a chemotherapeutic, a toxin, an inactive prodrug, a radiosensitizing agent, a photodynamic agent, a nucleic acid molecule or combinations thereof. 6. A method of treating an individual who has enterotoxin mediated diarrhea or who is at risk of contracting enterotoxin mediated diarrhea comprising the step of administering to said individual a compound of claim 1. 7. A method of claim 6 wherein R1 is Y, NTFY (SEQ ID NO:12), SSSNY (SEQ ID NO:9), SSDWDY (SEQ ID NO:10), ID, PN, or QE;R2 is a C cross linked to R6;R3 is C crosslinked to C at R8;R4 is E-L, or E-NmethylLeu;R5 is Leu or N(Me)-Leu;R6 is C cross linked to R2;R7 is a N-P-A;R8 is a C crosslinked to R3; andR9 is AGA or Y. 8. A compound of claim 1 wherein: R1 is a combination of 1-50 natural amino acids, 1-50 blocked amino acids, 1-50 synthetic amino acids, 1-50 derivatized amino acids; 1-50 amino acid mimetics, a 1-50 alkyls, one or more 1-50 substituted alkyls, one or more 1-50 aryls, one or more 1-50 substituted aryls, one or more 1-50 alkylaryls, one or more 1-50 substituted alkylaryls or combinations thereof; andR9 is a combination of 1-50 natural amino acids, 1-50 blocked amino acids, 1-50 synthetic amino acids, 1-50 derivatized amino acids; 1-50 amino acid mimetics, a 1-50 alkyls, one or more 1-50 substituted alkyls, one or more 1-50 aryls, one or more 1-50 substituted aryls, one or more 1-50 alkylaryls, one or more 1-50 substituted alkylaryls or combinations thereof. 9. A compound of claim 1 wherein: R1 is 0-20 amino acids; andR9 is 0-20 amino acids. 10. A compound of claim 9 wherein: R1 is Y, NTFY (SEQ ID NO:12), SSSNY (SEQ ID NO:9), SSDWDY (SEQ ID NO:10), ID, PN, or QE; andR9 is AGA or Y. 11. A compound of claim 1 wherein: R1 is 0-20 amino acids;R2 is cysteine, wherein R2 crosslinks with R6;R3 is cysteine, wherein R3 crosslinks with R8;R5 is a natural, blocked or derivatized leucine,R6 is a cysteine, wherein R6 crosslinks with R2;R8 is a cysteine, wherein R8 crosslinks with R3; andR9 is 0-20 amino acids. 12. A compound of claim 11 wherein: R1 is Y, NTFY (SEQ ID NO:12), SSSNY (SEQ ID NO:9), SSDWDY (SEQ ID NO:10), ID, PN, or QE; andR9 is AGA or Y. 13. A compound of claim 12 wherein: R5 is leucine. 14. A purified compound having a structure according to formula (I) R1-R2-R3-R4-R5-R6-R7-R8-R9 (I) wherein: R1 is Y, NTFY (SEQ ID NO:12), SSSNY (SEQ ID NO:9), SSDWDY (SEQ ID NO:10), ID, PN, or QE; andR2 is cysteine, wherein R2 crosslinks with R6;R3 is cysteine, wherein R3 crosslinks with R8;R4 is E-L wherein R4 forms a 310-helix turn group linking R3 to R5;R5 is leucine;R6 is a cysteine, wherein R6 crosslinks with R2;R7 is NPA wherein R7 forms a beta turn group linking R6 to R8;R8 is a cysteine, wherein R8 crosslinks with R3; andR9 is AGA or Y. 15. A compound of claim 14 wherein: R1 is Y; andR9 is Y. 16. A purified compound having a structure according to formula (I) R1-R2-R3-R4-R5-R6-R7-R8-R9 (I) wherein: R1 is a combination of 1-50 natural amino acids, 1-50 blocked amino acids, 1-50 synthetic amino acids, 1-50 derivatized amino acids; 1-50 amino acid mimetics, a 1-50 alkyls, one or more 1-50 substituted alkyls, one or more 1-50 aryls, one or more 1-50 substituted aryls, one or more 1-50 alkylaryls, one or more 1-50 substituted alkylaryls or combinations thereof;R2 is a natural, blocked, or derivatized cysteine, wherein R2 crosslinks with R6;R3 is a natural, blocked, or derivatized cysteine, wherein R3 crosslinks with R8;R4 is E-L wherein R4 forms a 310-helix turn group linking R3 to R5;R5 is a natural, blocked or derivatized leucine, or a natural, blocked or derivatized isoleucine,R6 is a natural, blocked, or derivatized cysteine, wherein R6 crosslinks with R2;R7 is NPA wherein R7 forms a beta turn group linking R6 to R8;R8 is a natural, blocked, or derivatized cysteine, wherein R8 crosslinks with R3; andR9 is a combination of 1-50 natural amino acids, 1-50 blocked amino acids, 1-50 synthetic amino acids, 1-50 derivatized amino acids; 1-50 amino acid mimetics, a 1-50 alkyls, one or more 1-50 substituted alkyls, one or more 1-50 aryls, one or more 1-50 substituted aryls, one or more 1-50 alkylaryls, one or more 1-50 substituted alkylaryls or combinations thereof. 17. A purified compound having a structure according to formula (I) R1-R2-R3-R4-R5-R6-R7-R8-R9 (I) wherein: R1 is 0-20 amino acids;R2 is a natural, blocked, or derivatized cysteine, wherein R2 crosslinks with R6;R3 is a natural, blocked, or derivatized cysteine, wherein R3 crosslinks with R8;R4 is E-L wherein R4 forms a 310-helix turn group linking R3 to R5;R5 is a natural, blocked or derivatized leucine, or a natural, blocked or derivatized isoleucine,R6 is a natural, blocked, or derivatized cysteine, wherein R6 crosslinks with R2;R7 is NPA wherein R7 forms a beta turn group linking R6 to R8;R8 is a natural, blocked, or derivatized cysteine, wherein R8 crosslinks with R3; andR9 is 0-20 amino acids. 18. A purified compound having a structure according to formula (I) R1-R2-R3-R4-R5-R6-R7-R8-R9 (I) wherein: R1 is Y, NTFY (SEQ ID NO:12), SSSNY (SEQ ID NO:9), SSDWDY (SEQ ID NO:10), ID, PN, or QE;R2 is a natural, blocked, or derivatized cysteine, wherein R2 crosslinks with R6;R3 is a natural, blocked, or derivatized cysteine, wherein R3 crosslinks with R8;R4 is E-L wherein R4 forms a 310-helix turn group linking R3 to R5;R5 is a natural, blocked or derivatized leucine, or a natural, blocked or derivatized isoleucine,R6 is a natural, blocked, or derivatized cysteine, wherein R6 crosslinks with R2;R7 is NPA wherein R7 forms a beta turn group linking R6 to R8;R8 is a natural, blocked, or derivatized cysteine, wherein R8 crosslinks with R3; andR9 is AGA or Y. 19. A purified compound having a structure according to formula (I) R1-R2-R3-R4-R5-R6-R7-R8-R9 (I) wherein: R1 is 0-20 amino acids;R2 is cysteine, wherein R2 crosslinks with R6;R3 is cysteine, wherein R3 crosslinks with R8;R4 is E-L wherein R4 forms a 310-helix turn group linking R3 to R5;R5 is a natural, blocked or derivatized leucine,R6 is a cysteine, wherein R6 crosslinks with R2;R7 is NPA wherein R7 forms a beta turn group linking R6 to R8;R8 is a cysteine, wherein R8 crosslinks with R3; andR9 is 0-20 amino acids. 20. A purified compound having a structure according to formula (I) R1-R2-R3-R4-R5-R6-R7-R8-R9 (I) wherein: R1 is Y, NTFY (SEQ ID NO:12), SSSNY (SEQ ID NO:9), SSDWDY (SEQ ID NO:10), ID, PN, or QE;R2 is cysteine, wherein R2 crosslinks with R6;R3 is cysteine, wherein R3 crosslinks with R8;R4 is E-L wherein R4 forms a 310-helix turn group linking R3 to R5;R5 is a natural, blocked or derivatized leucine,R6 is a cysteine, wherein R6 crosslinks with R2;R7 is NPA wherein R7 forms a beta turn group linking R6 to R8;R8 is a cysteine, wherein R8 crosslinks with R3; andR9 is AGA or Y. 21. A purified compound having a structure according to formula (I) R1-R2-R3-R4-R5-R6-R7-R8-R9 (I) wherein: R1 is Y, NTFY (SEQ ID NO:12), SSSNY (SEQ ID NO:9), SSDWDY (SEQ ID NO:10), ID, PN, or QE;R2 is cysteine, wherein R2 crosslinks with R6;R3 is cysteine, wherein R3 crosslinks with R8;R4 is E-L wherein R4 forms a 310-helix turn group linking R3 to R5;R5 is leucine,R6 is a cysteine, wherein R6 crosslinks with R2;R7 is NPA wherein R7 forms a beta turn group linking R6 to R8;R8 is a cysteine, wherein R8 crosslinks with R3; andR9 is AGA or Y.
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