Cyclic peptide conjugates and methods of use

Patent metadata

Field	Value
Publication number	US-2016229892-A1
Application number	US-201415024928-A
Country	US
Kind code	A1
Filing date	Sep 26, 2014
Priority date	Sep 27, 2013
Publication date	Aug 11, 2016
Grant date	—

Abstract

The present invention concerns cyclic compounds, compositions comprising the cyclic compounds, linkers, a method of preparing a carrying agent:cyclic compound adduct, a method for treating disorders such as proliferation disorders (e.g., malignancies), bone deficiency diseases, and autoimmune diseases, and a method for suppressing the growth of, or inducing apoptosis in, cells (e.g., malignant cells).

First claim

1 . A cyclic compound, comprising a recognition sequence and a non-recognition sequence, wherein said recognition sequence comprises at least four amino acids, wherein said non-recognition sequence comprises at least four amino acids, and wherein said recognition sequence is joined to said non-recognition sequence by a first linker and a second linker, wherein said first linker and said second linker are independently selected from the structures:

(D-Pro-L-Pro);

(methylsulfonamido aminoethylglycine);

((pyrrolidin-2-ylmethoxy)acetate),

((pyrrolidin-2-ylmeththiyl)acetate);

(substituted sulfonamide aminoethylglycine); or

wherein R is a substituted or unsubstituted C 2 -C 30 alkyl, aryl, alkylaryl, or arylalky group; wherein at least one of said first linker and said second linker is,

(N-(pyrrolidin-2-ylmethyl substituted sulfamido glycine), wherein at least one R is:

wherein x is 1-12, y is 1-12, R′ is

or absent, z is 1 to 20, and X comprises a carrying agent.

2 . The cyclic compound of claim 1 , wherein said non-recognition sequence is five amino acids selected from KLQLK (SEQ ID NO: 1), QLKLK (SEQ ID NO:2), KQKLK (SEQ ID NO:3), KXKXK (SEQ ID NO:4), or ELKLK (SEQ ID NO:5) wherein X=sarcosine and the recognition sequence is five amino acids selected from WAVAW (SEQ ID NO:6), WAVAA (SEQ ID NO:7), WAVAM (SEQ ID NO:8), WAVAN* (SEQ ID NO:9), WAVVN* (SEQ ID NO:10), WAVSN* (SEQ ID NO:11), WAAAW (SEQ ID NO:12), WAAAA (SEQ ID NO:13), WAAAM (SEQ ID NO:14), WAAAN* (SEQ ID NO:15), WAAVW (SEQ ID NO:16), WAAVA (SEQ ID NO:17), WAAVM (SEQ ID NO:18), WAAVN* (SEQ ID NO:19), WAASN* (SEQ ID NO:20), WVVAW (SEQ ID NO:21), WVVAA (SEQ ID NO:22), WVVAM (SEQ ID NO:23), WVVAN* (SEQ ID NO:24), WVVVW (SEQ ID NO:25), WVVVA (SEQ ID NO:26), WVVVM (SEQ ID NO:27), WVVVN* (SEQ ID NO:28), WVVSN* (SEQ ID NO:29), WVAAN* (SEQ ID NO:30), WVAVW (SEQ ID NO:31), WVAVA (SEQ ID NO:32), WVAVM (SEQ ID NO:33), WVAVN* (SEQ ID NO:34), WVASN* (SEQ ID NO:35), WSVAW (SEQ ID NO:36), WSVAA (SEQ ID NO:37), WSVAM (SEQ ID NO:38), WSVAN* (SEQ ID NO:39), WSVVW (SEQ ID NO:40), WSVVA (SEQ ID NO:41), WSVVM (SEQ ID NO:42), WSVVN* (SEQ ID NO:43), WSVSW (SEQ ID NO:44), WSVSA (SEQ ID NO:45), WSVSM (SEQ ID NO:46), WSVSN* (SEQ ID NO:47), WSAAW (SEQ ID NO:48), WSAAA (SEQ ID NO:49), WSAAM (SEQ ID NO:50), WSAAN* (SEQ ID NO:51), WSAVW (SEQ ID NO:52), WSAVA (SEQ ID NO:53), WSAVM (SEQ ID NO:54), WSAVN* (SEQ ID NO:55), WSASW (SEQ ID NO:56), WSASA (SEQ ID NO:57), WSASM (SEQ ID NO:58), WSASN* (SEQ ID NO:59), WYVAW (SEQ ID NO:60), WYVAA (SEQ ID NO:61), WYVAM (SEQ ID NO:62), WYVAN* (SEQ ID NO:63), WYVVW (SEQ ID NO:64), WYVVA (SEQ ID NO:65), WYVVM (SEQ ID NO:66), WYVVN* (SEQ ID NO:67), WYVSW (SEQ ID NO:68), WYVSA (SEQ ID NO:69), WYVSM (SEQ ID NO:70), WYVSN* (SEQ ID NO:71), WYAAW (SEQ ID NO:72), WYAAA (SEQ ID NO:73), WYAAM (SEQ ID NO:74), WYAAN* (SEQ ID NO:75), WYAVW (SEQ ID NO:76), WYAVA (SEQ ID NO:77), WYAVM (SEQ ID NO:78), WYAVN* (SEQ ID NO:79), WYASW (SEQ ID NO:80), WYASA (SEQ ID NO:81), WYASM (SEQ ID NO:82), WYASN* (SEQ ID NO:83), AAVAA (SEQ ID NO:84), AAVAM (SEQ ID NO:85), AAVAN* (SEQ ID NO:86), AAVVN* (SEQ ID NO:87), AAVSN* (SEQ ID NO:88), AAAAA (SEQ ID NO:89), AAAAM (SEQ ID NO:90), AAAAN* (SEQ ID NO:91), AAAVW (SEQ ID NO:92), AAAVA (SEQ ID NO:93), AAAVM (SEQ ID NO:94), AAAVN* (SEQ ID NO:95), AAASM (SEQ ID NO:96), AAASN* (SEQ ID NO:97), AVVAW (SEQ ID NO:98), AVVAA (SEQ ID NO:99), AVVAM (SEQ ID NO:100), AVVAN* (SEQ ID NO: 101), AVVVA (SEQ ID NO: 102), AVVVM (SEQ ID NO: 103), AVVVN* (SEQ ID NO: 104), AVVSN* (SEQ ID NO: 105), AVAAW (SEQ ID NO: 106), AVAAM (SEQ ID NO: 107), AVAAN* (SEQ ID NO: 108), AVAVA (SEQ ID NO: 109), AVAVM (SEQ ID NO: 110), AVAVN* (SEQ ID NO:111), AVASN* (SEQ ID NO:112), ASVAW (SEQ ID NO:113), ASVAA (SEQ ID NO: 114), ASVAM (SEQ ID NO:115), ASVAN* (SEQ ID NO: 116), ASVVW (SEQ ID NO: 117), ASVVA (SEQ ID NO:118), ASVVM (SEQ ID NO:119), ASVVN* (SEQ ID NO:120), ASVSA (SEQ ID NO:121), ASVSM (SEQ ID NO:122), ASVSN* (SEQ ID NO:123), ASAAW (SEQ ID NO:124), ASAAA (SEQ ID NO:125), ASAAM (SEQ ID NO:126), ASAAN* (SEQ ID NO:127), ASAVW (SEQ ID NO:128), ASAVA (SEQ ID NO:129), ASAVM (SEQ ID NO:130), ASAVN* (SEQ ID NO:131), ASASA (SEQ ID NO:132), ASASM (SEQ ID NO:133), ASASN* (SEQ ID NO: 134), AYVAW (SEQ ID NO: 135), AYVAA (SEQ ID NO: 136), AYVAM (SEQ ID NO: 137), AYVAN* (SEQ ID NO: 138), AYVVW (SEQ ID NO: 139), AYVVA (SEQ ID NO: 140), AYVVM (SEQ ID NO:141), AYVVN* (SEQ ID NO:142), AYVSW (SEQ ID NO:143), AYVSA (SEQ ID NO: 144), AYVSM (SEQ ID NO: 145), AYVSN* (SEQ ID NO: 146), AYAAW (SEQ ID NO: 147), AYAAA (SEQ ID NO: 148), AYAAM (SEQ ID NO: 149), AYAAN* (SEQ ID NO: 150), AYAVW (SEQ ID NO: 151), AYAVA (SEQ ID NO: 152), AYAVM (SEQ ID NO: 153), AYAVN* (SEQ ID NO:154), AYASW (SEQ ID NO:155), AYASA (SEQ ID NO:156), AYASM (SEQ ID NO:157), AYASN* (SEQ ID NO:158), MAVAA (SEQ ID NO:159), MAVAM (SEQ ID NO: 160), MAVAN* (SEQ ID NO: 161), MAVVN* (SEQ ID NO: 162), MAVSN* (SEQ ID NO: 163), MAAAA (SEQ ID NO: 164), MAAAM (SEQ ID NO: 165), MAAAN* (SEQ ID NO: 166), MAAVW (SEQ ID NO: 167), MAAVA (SEQ ID NO: 168), MAAVM (SEQ ID NO: 169), MAAVN* (SEQ ID NO:170), MAASN* (SEQ ID NO: 171), MVVAW (SEQ ID NO: 172), MVVAA (SEQ ID NO: 173), MVVAM (SEQ ID NO:174), MVVAN* (SEQ ID NO:175), MVVVM (SEQ ID NO:176), MVVVN* (SEQ ID NO: 177), MVVSN* (SEQ ID NO: 178), MVAAM (SEQ ID NO: 179), MVAAN* (SEQ ID NO:180), MVAVM (SEQ ID NO: 181), MVAVN* (SEQ ID NO: 182), MVASN* (SEQ ID NO: 183), MSVAW (SEQ ID NO: 184), MSVAA (SEQ ID NO: 185), MSVAM (SEQ ID NO: 186), MSVAN* (SEQ ID NO: 187), MSVVW (SEQ ID NO: 188), MSVVA (SEQ ID NO: 189), MSVVM (SEQ ID NO: 190), MSVVN* (SEQ ID NO: 191), MSVSM (SEQ ID NO: 192), MSVSN* (SEQ ID NO: 193), MSAAW (SEQ ID NO: 194), MSAAA (SEQ ID NO: 195), MSAAM (SEQ ID NO: 196), MSAAN* (SEQ ID NO: 197), MSAVW (SEQ ID NO: 198), MSAVA (SEQ ID NO: 199), MSAVM (SEQ ID NO:200), MSAVN* (SEQ ID NO:201), MSASM (SEQ ID NO:202), MSASN* (SEQ ID NO:203), MYVAW (SEQ ID NO:204), MYVAA (SEQ ID NO:205), MYVAM (SEQ ID NO:206), MYVAN* (SEQ ID NO:207), MYVVW (SEQ ID NO:208), MYVVA (SEQ ID NO:209), MYVVM (SEQ ID NO:210), MYVVN* (SEQ ID NO:211), MYVSW (SEQ ID NO:212), MYVSA (SEQ ID NO:213), MYVSM (SEQ ID NO:214), MYVSN* (SEQ ID NO:215), MYAAW (SEQ ID NO:216), MYAAA (SEQ ID NO:217), MYAAM (SEQ ID NO:218), MYAAN* (SEQ ID NO:219), MYAVW (SEQ ID NO:220), MYAVA (SEQ ID NO:221), MYAVM (SEQ ID NO:222), MYAVN* (SEQ ID NO:223), MYASW (SEQ ID NO:224), MYASA (SEQ ID NO:225), MYASM (SEQ ID NO:226), or MYASN* (SEQ ID NO:227), wherein N*=norleucine, and wherein either end of said recognition sequence can be a N-terminus.

3 . The cyclic compound of claim 1 , wherein one R is:

4 . The cyclic compound of claim 1 , wherein R is H, C 1 -C 30 alkyl, C 2 -C 30 alkenyl, C 2 -C 30 alkynyl, C 6 -C 14 aryl, C 7 -C 30 arylalkyl, C 8 -C 30 arylalkenyl, C 8 -C 30 arylalkynyl, hydroxy, C 1 -C 30 alkoxy, C 6 -C 14 aryloxy, C

Assignees

• H Lee Moffitt Cancer Ct & Res
• Univ South Florida
• The Scripps Res Inst Office Of Patent Counsel Tpc8
• Modulation Therapeutics

Inventors

• Hazlehurst Lori
• Rader Christoph
• Li Xiuling
• Mclaughlin Mark

Classifications

• C07K7/08 Primary

  having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68) · CPC title

• C07K1/00

  General methods for the preparation of peptides {, i.e. processes for the organic chemical preparation of peptides or proteins of any length} · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• C07K7/06 Primary

  having 5 to 11 amino acids · CPC title

• C07K14/70596

  Molecules with a "CD"-designation not provided for elsewhere · CPC title