Immunoproteasome β5i-Selective Dipeptidomimetic Inhibitors.
Immunoproteasome β5i-Selective Dipeptidomimetic Inhibitors.
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DOI：
10.1002/cmdc.201600384
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发表时间：
2016-10-06
期刊：
影响因子：
3.4
通讯作者：
Lin G
中科院分区：
文献类型：
--
作者：
Singh PK;Fan H;Jiang X;Shi L;Nathan CF;Lin G
N,C-capped dipeptides belong to a class of noncovalent proteasome inhibitors. Here we report that insertion of a β-amino acid in N,C-capped dipeptides markedly reduces the inhibitory potency against human constitutive proteasome, yet maintains potent inhibitory activity against human immunoproteasome, thus achieving thousands-fold selectivity for β5i over β5c. Structure-activity relationship studies reveal that β5c does not tolerate the β-amino acid based dipeptidomimetics as β5i does. In vitro, one such compound inhibited human T cell proliferation. Compounds of this class may have potential as therapeutics for autoimmune and inflammatory diseases with less mechanism-based cytotoxicity than agents that also inhibit the constitutive proteasome. Class-wide selective inhibitors for immunoproteasome β5i over constitutive proteasome β5c were serendipitously identified by incorporating β-amino acids into dipeptides, of which one compound inhibited T cell proliferation.
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影响因子：
64.8
作者：
Kim, Min-Sik;Pinto, Sneha M.;Getnet, Derese;Nirujogi, Raja Sekhar;Manda, Srikanth S.;Chaerkady, Raghothama;Madugundu, Anil K.;Kelkar, Dhanashree S.;Isserlin, Ruth;Jain, Shobhit;Thomas, Joji K.;Muthusamy, Babylakshmi;Leal-Rojas, Pamela;Kumar, Praveen;Sahasrabuddhe, Nandini A.;Balakrishnan, Lavanya;Advani, Jayshree;George, Bijesh;Renuse, Santosh;Selvan, Lakshmi Dhevi N.;Patil, Arun H.;Nanjappa, Vishalakshi;Radhakrishnan, Aneesha;Prasad, Samarjeet;Subbannayya, Tejaswini;Raju, Rajesh;Kumar, Manish;Sreenivasamurthy, Sreelakshmi K.;Marimuthu, Arivusudar;Sathe, Gajanan J.;Chavan, Sandip;Datta, Keshava K.;Subbannayya, Yashwanth;Sahu, Apeksha;Yelamanchi, Soujanya D.;Jayaram, Savita;Rajagopalan, Pavithra;Sharma, Jyoti;Murthy, Krishna R.;Syed, Nazia;Goel, Renu;Khan, Aafaque A.;Ahmad, Sartaj;Dey, Gourav;Mudgal, Keshav;Chatterjee, Aditi;Huang, Tai-Chung;Zhong, Jun;Wu, Xinyan;Shaw, Patrick G.;Freed, Donald;Zahari, Muhammad S.;Mukherjee, Kanchan K.;Shankar, Subramanian;Mahadevan, Anita;Lam, Henry;Mitchell, Christopher J.;Shankar, Susarla Krishna;Satishchandra, Parthasarathy;Schroeder, John T.;Sirdeshmukh, Ravi;Maitra, Anirban;Leach, Steven D.;Drake, Charles G.;Halushka, Marc K.;Prasad, T. S. Keshava;Hruban, Ralph H.;Kerr, Candace L.;Bader, Gary D.;Iacobuzio-Donahue, Christine A.;Gowda, Harsha;Pandey, Akhilesh
通讯作者：
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影响因子：
82.9
作者：
Muchamuel, Tony;Basler, Michael;Groettrup, Marcus
通讯作者：
Groettrup, Marcus
影响因子：
3.6
作者：
Hu, GQ;Lin, G;Li, HL
通讯作者：
Li, HL
影响因子：
16.6
作者：
de Bruin, Gerjan;Xin, Bo Tao;Overkleeft, Herman S.
通讯作者：
Overkleeft, Herman S.
影响因子：
30.5
作者：
Kincaid, Eleanor Z.;Che, Jenny W.;York, Ian;Escobar, Hernando;Reyes-Vargas, Eduardo;Delgado, Julio C.;Welsh, Raymond M.;Karow, Margaret L.;Murphy, Andrew J.;Valenzuela, David M.;Yancopoulos, George D.;Rock, Kenneth L.
通讯作者：
Rock, Kenneth L.