0 15 Affinity-driven affinity-driven JJ 16 23 peptide peptide NN 24 33 selection selection NN 34 36 of of IN 37 39 an an DT 40 44 NFAT NFAT NNP 45 54 inhibitor inhibitor NN 55 59 more more RBR 60 69 selective selective JJ 70 74 than than IN 75 86 cyclosporin cyclosporin NN 87 88 A a NN 89 90 [ [ ( 90 93 see see VB 94 102 comments comment NNS 102 103 ] ] ) 105 108 The the DT 109 113 flow flow NN 114 116 of of IN 117 128 information information NN 129 133 from from IN 134 152 calcium-mobilizing calcium-mobilizing JJ 153 162 receptors receptor NNS 163 165 to to TO 166 173 nuclear nuclear JJ 174 180 factor factor NN 181 183 of of IN 184 193 activated activate VBN 194 195 T t NN 196 201 cells cell NNS 202 203 ( ( ( 203 218 NFAT)-dependent nfat)-dependent JJ 219 224 genes gene NNS 225 227 is be VBZ 228 238 critically critically RB 239 248 dependent dependent JJ 249 251 on on IN 252 263 interaction interaction NN 264 271 between between IN 272 275 the the DT 276 287 phosphatase phosphatase NN 288 299 calcineurin calcineurin NN 300 303 and and CC 304 307 the the DT 308 321 transcription transcription NN 322 328 factor factor NN 329 333 NFAT nfat NN 333 334 . . . 335 336 A a DT 337 350 high-affinity high-affinity JJ 351 370 calcineurin-binding calcineurin-binding JJ 371 378 peptide peptide NN 379 382 was be VBD 383 391 selected select VBN 392 396 from from IN 397 410 combinatorial combinatorial JJ 411 418 peptide peptide NN 419 428 libraries library NNS 429 434 based base VBN 435 437 on on IN 438 441 the the DT 442 453 calcineurin calcineurin NN 454 461 docking docking NN 462 467 motif motif NN 468 470 of of IN 471 475 NFAT NFAT NNP 475 476 . . . 477 481 This this DT 482 489 peptide peptide NN 490 498 potently potently RB 499 508 inhibited inhibit VBD 509 513 NFAT nfat NN 514 524 activation activation NN 525 528 and and CC 529 543 NFAT-dependent nfat-dependent JJ 544 554 expression expression NN 555 557 of of IN 558 568 endogenous endogenous JJ 569 577 cytokine cytokine NN 578 583 genes gene NNS 584 586 in in IN 587 588 T t NN 589 594 cells cell NNS 594 595 , , , 596 603 without without IN 604 613 affecting affect VBG 614 617 the the DT 618 628 expression expression NN 629 631 of of IN 632 637 other other JJ 638 647 cytokines cytokine NNS 648 652 that that WDT 653 660 require require VBP 661 672 calcineurin calcineurin NN 673 676 but but CC 677 680 not not RB 681 685 NFAT NFAT NNP 685 686 . . . 687 699 Substitution substitution NN 700 702 of of IN 703 706 the the DT 707 716 optimized optimize VBN 717 724 peptide peptide NN 725 733 sequence sequence NN 734 738 into into IN 739 742 the the DT 743 750 natural natural JJ 751 762 calcineurin calcineurin NN 763 770 docking docking NN 771 775 site site NN 776 785 increased increase VBD 786 789 the the DT 790 801 calcineurin calcineurin NN 802 816 responsiveness responsiveness NN 817 819 of of IN 820 824 NFAT NFAT NNP 824 825 . . . 826 835 Compounds compound NNS 836 840 that that WDT 841 850 interfere interfere VBP 851 862 selectively selectively RB 863 867 with with IN 868 871 the the DT 872 888 calcineurin-NFAT calcineurin-nfat NN 889 900 interaction interaction NN 901 908 without without IN 909 918 affecting affect VBG 919 930 calcineurin calcineurin NN 931 942 phosphatase phosphatase NN 943 951 activity activity NN 952 955 may may MD 956 958 be be VB 959 965 useful useful JJ 966 968 as as IN 969 980 therapeutic therapeutic JJ 981 987 agents agent NNS 988 992 that that WDT 993 996 are be VBP 997 1001 less less RBR 1002 1007 toxic toxic JJ 1008 1012 than than IN 1013 1020 current current JJ 1021 1026 drugs drug NNS 1026 1027 . . .