Arg-Serpin human plasminogen activator inhibitor designated PAI-2
AssigneesNew England Medical Center Hospitals, Inc., Tufts College, Wellesley College, Mit
InventorsAndrew C. Webb, Philip E. Auron
Life of this patent
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Abstract
The invention is directed to an Arg-Serpin human plasminogen activator inhibitor designated PAI-2. This protein is prepared via recombinant DNA means. The invention also includes other serpins which can be made by amino acid substitutions or deletions in conserved regions of PAI-1 and PAI-2, as shown in FIG. 4. The proteins of the invention can be used to inhibit, or at least modulate, human plasminogen activator activity in a variety of physiological conditions, e.g., fibrinolysis, tumor metastasis, and tumor growth.
Claims13
Recombinant DNA coding for human precursor PAI-2 comprising the following amino acid sequence:
- ______________________________________ 1 MED LCVANTLFALNLF 16 17 KHLAKASPTQNLFLSPWSIS 36 37 STMAMVYMG SRG STED QMAK 56 57 VLQFNEVG ANAVTPMTPENF 76 77 TSCG FMQQIQKG SYPD AILQ 96 97 AQAAD KIHSSFRSLSSAINA 116 117 STG NYLLESVNKLFG EKSAS 136 137 FREEYIRLCQKYYSSEPQAV 156 157 D FLECAEEARKKIN SWVKTQ 176 177 TKG KIPNLLPEG SVD G D TRM 196 197 VLVNAVYFKG KWKTPFEKKL 216 217 NG LYPFRVNSAQRTPVQMMY 236 237 LREKLNIG YIED LKAQILEL 256 257 PYAG D VSMFLLLPD EIAD VS 276 277 TG LELLESEITYD KLNKWTS 296 297 KD KMAED EVEVYIPQFKLEE 316 317 HYELRSILRSMG MED AFNKG 336 337 RANFSG MSERND LFLS EVFH 356 357 QAMVD VNEEG TEAAAG TG G V 376 377 MTG RTG HG G PQFVAD HPFLF 396 397 LIMHKITNCILFFG RFSSP. 415 ______________________________________
A DNA transfer vector comprising a gene coding for human precursor PAI-2 comprising the following amino acid sequence:
- ______________________________________ 1 MED LCVANTLFALNLF 16 17 KHLAKASPTQNLFLSPWSIS 36 37 STMAMVYMG SRG STED QMAK 56 57 VLQFNEVG ANAVTPMTPENF 76 77 TSCG FMQQIQKG SYPD AILQ 96 97 AQAAD KIHSSFRSLSSAINA 116 117 STG NYLLESVNKLFG EKSAS 136 137 FREEYIRLCQKYYSSEPQAV 156 157 D FLECAEEARKKIN SWVKTQ 176 177 TKG KIPNLLPEG SVD G D TRM 196 197 VLVNAVYFKG KWKTPFEKKL 216 217 NG LYPFRVNSAQRTPVQMMY 236 237 LREKLNIG YIED LKAQILEL 256 257 PYAG D VSMFLLLPD EIAD VS 276 277 TG LELLESEITYD KLNKWTS 296 297 KD KMAED EVEVYIPQFKLEE 316 317 HYELRSILRSMG MED AFNKG 336 337 RANFSG MSERND LFLS EVFH 356 357 QAMVD VNEEG TEAAAG TG G V 376 377 MTG RTG HG G PQFVAD HPFLF 396 397 LIMHKITNCILFFG RFSSP. 415 ______________________________________
A DNA transfer vector comprising a gene coding for human mature PAI-2 containing DNA encoding methionine immediately preceding the serine residue at position 23 in the precursor PAI-2 DNA sequence.
Recombinant DNA coding for human mature PAI-2 comprising the following amino acid sequence:
- ______________________________________ 23 SPTQNLFLSPWSIS 36 37 STMAMVYMG SRG STED QMAK 56 57 VLQFNEVG ANAVTPMTPENF 76 77 TSCG FMQQIQKG SYPD AILQ 96 97 AQAAD KIHSSFRSLSSAINA 116 117 STG NYLLESVNKLFG EKSAS 136 137 FREEYIRLCQKYYSSEPQAV 156 157 D FLECAEEARKKINSWVKTQ 176 177 TKG KIPNLLPEG SVD G D TRM 196 197 VLVNAVYFKG KWKTPFEKKL 216 217 NG LYPFRVNSAQRTPVQMMY 236 237 LREKLNIG YIED LKAQILEL 256 257 PYAG D VSMFLLLPD EIAD VS 276 277 TG LELLESEITYD KLNKWTS 296 297 KD KMAED EVEVYIPQFKLEE 316 317 HYELRSILRSMG MED AFNKG 336 337 RANFSG MSERND LFLSEVFH 356 357 QAMVD VNEEG TEAAAG TG G V 376 377 MTG RTG HG G PQFVAD HPFLF 396 397 LIMHKITNCILFFG RFSSP. 415
A DNA transfer vector comprising a gene coding for human mature PAI-2 in association with a signal peptide sequence, wherein said gene comprises DNA coding for the following amino acid sequence:
- ______________________________________ 23 SPTQNLFLSPWSIS 36 37 STMAMVYMG SRG STED QMAK 56 57 VLQFNEVG ANAVTPMTPENF 76 77 TSCG FMQQIQKG SYPD AILQ 96 97 AQAAD KIHSSFRSLSSAINA 116 117 STG NYLLESVNKLFG EKSAS 136 137 FREEYIRLCQKYYSSEPQAV 156 157 D FLECAEEARKKINSWVKTQ 176 177 TKG KIPNLLPEG SVD G D TRM 196 197 VLVNAVYFKG KWKTPFEKKL 216 217 NG LYPFRVNSAQRTPVQMMY 236 237 LREKLNIG YIED LKAQILEL 256 257 PYAG D VSMFLLLPD EIAD VS 276 277 TG LELLESEITYD KLNKWTS 296 297 KD KMAED EVEVYIPQFKLEE 316 317 HYELRSILRSMG MED AFNKG 336 337 RANFSG MSERND LFLSEVFH 356 357 QAMVD VNEEG TEAAAG TG G V 376 377 MTG RTG HG G PQFVAD HPFLF 396 397 LIMHKITNCILFFG RFSSP. 415
A process for preparing PAI-2 which comprises culturing a prokaryotic or eukaryotic host hosting a recombinant DNA transfer vector comprising DNA coding for PAI-2.
The microorganism E. coli HB101(pcD-1214).
Dependencies are inferred from the claim text.