USRE37462EExpiredUtility
Protein sequence of the plant toxin gelonin
Est. expiryAug 14, 2010(expired)· nominal 20-yr term from priority
C07K 14/415A61P 35/00C12N 15/62A61P 31/00C07K 2319/55A61P 37/06C07K 14/00
71
PatentIndex Score
20
Cited by
42
References
18
Claims
Abstract
This invention relates to substantially purified gelonin, toxic fragments thereof, the DNA sequences encoding gelonin and use of the DNA for producing, by recombinant technology, gelonin, toxic fragments thereof and fusion proteins. More specifically, the invention relates to the primary amino acid sequence of gelonin, and of the DNA encoding said gelonin and the production of synthetic gelonin and toxic fragments thereof.
Claims
exact text as granted — not AI-modifiedWhat is claimed as new and is desired to be covered under Letters Patent is:
1. Substantially pure gelonin toxin having the amino acid sequence:
GlyLeuAspThrValSerPheSerThrLys
10
GlyAlaThrTyrIleThrTyrValAsnPhe
20
LeuAsnGluLeuArgValLysLeuLysPro
30
GluGlyAsnSerHisGlyIleProLeuLeu
40
ArgLysGlyAspAspProGlyLysCysPhe
50
ValLeuValAlaLeuSerAsnAspAsnGly
60
GlnLeuAlaGluIleAlaIleAspValThr
70
SerValTyrValValGlyTyrGlnValArg
80
AsnArgSerTyrPhePheLysAspAlaPro
90
AspAlaAlaTyrGluGlyLeuPheLysAsn
100
ThrIleLysAsnProLeuLeuPheGlyGly
110
LysThrArgLeuHisPheGlyGlySerTyr
120
ProSerLeuGluGlyGluLysAlaTyrArg
130
GluThrThrAspLeuGlyIleGluProLeu
140
ArgIleGlyIleLysLysLeuAspGluAsn
150
AlaIleAspAsnTyrLysProThrGluIle
160
AlaSerSerLeuLeuValValIleGlnMet
170
ValSerGluAlaAlaArgPheThrPheIle
180
GluAsnGlnIleArgAsnAsnPheGlnGln
190
ArgIleArgProAlaAsnAsnThrIleSer
200
LeuGlnAsnLysTrpGlyLysLeuSerPhe
210
GlnIleArgThrSerGlyAlaAsnGlyMet
220
PheSerGluAlaValGluLeuGluArgAla
230
AsnGlyLysLysTyrTyrValThrAlaVal
240
AspGlnValLysProLysIleAlaLeuLeu
250
LysPheValAspLysAspProGlu
260
or a fragment or derivative thereof, said fragment or derivative having an activity which inhibits cellular protein synthesis but does not bind to a cell surface receptor.
2. A DNA sequence of the formula:
GGNYTNGAYA CNGTNWSNTT YWSNACNAAR GGNGCNACNT AYATHACNTA YGTNAAYTTY
60
YTNAAYGARY TNMGNGTNAA RYTNAARCCN GARGGNAAYW SNCAYGGNAT HCCNYTNYTN
120
MGNAARGGNG AYGAYCCNGG NAARTGYTTY GTNYTNGTNG CNYTNWSNAA YGAYAAYGGN
180
CARYTNGCNG ARATHGCNAT HGAYGTNACN WSNGTNTAYG TNGTNGGNTA YCARGTNMGN
240
AAYMGNWSNT AYTTYTTYAA RGAYGCNCCN GAYGCNGCNT AYGARGGNYT NTTYAATAAY
300
ACNATHAARA AYCCNYTNYT NTTYGGNGGN AARACNMGNY TNCAYTTYGG NGGNWSNTAY
360
CCNWSNYTNG ARGGNGARAA RGCNTAYMGN GARACNACNG AYYTNGGNAT HGARCCNYTN
420
MGNATHGGNA THAATAARYT NGAYGARAAY GCNATHGAYA AYTAYAARCC NACNGARATH
480
GCNWSNWSNY TNYTNGTNGT NATHCARATG GTNWSNGARG CNGCNMGNTT YACNTTYATH
540
GARAAYCARA THMGNAAYAA YTTYCARCAR MGNATHMGNC CNGCNAAYAA YACNATHWSN
600
YTNGARAAYA ARTGGGGNAA RYTNWSNTTY CARATHMGNA CNWSNGGNGC NAAYGGNATG
660
TTYWSNGARG CNGTNGARYT NGARMGNGCN AAYGGNAARA ARTAYTAYGT NACNGCNGTN
720
GAYCARGTNA ARCCNAARAT HGCNYTNYTN AARTTYGTNG AYAARGAYCC NGAR
774
wherein
R = A or G
K = G or T
N = any
Y = C or T
M = A or C
S = C or G
B = C, G, or T
V = A, C, or G
W = A or T
D = A, G, or T
H = A, C, or T
X = unknown
or a fragment or derivative thereof, said fragment or derivative coding for gelonin or for a polypeptide having an activity which inhibits cellular protein synthesis but does not bind to a cell surface receptor.
3. The toxin of claim 1 further defined as having the amino acid sequence:
GlyLeuAspThrValSerPheSerThrLys
GlyAlaThrTyrIleThrTyrValAsnPhe
LeuAsnGluLeuArgValLysLeuLysPro
GluGlyAsnSerHisGlyIleProLeuLeu
ArgLysGlyAspAspProGlyLysCysPhe
ValLeuValAlaLeuSerAsnAspAsnGly
GlnLeuAlaGluIleAlaIleAspValThr
SerValTyrValValGlyTyrGlnValArg
AsnArgSerTyrPhePheLysAspAlaPro
AspAlaAlaTyrGluGlyLeuPheLysAsn
ThrIleLysAsnProLeuLeuPheGlyGly
LysThrArgLeuHisPheGlyGlySerTyr
ProSerLeuGluGlyGluLysAlaTyrArg
GluThrThrAspLeuGlyIleGluProLeu
ArgIleGlyIleLysLysLeuAspGluAsn
AlaIleAspAsnTyrLysProThrGluIle
AlaSerSerLeuLeuValValIleGlnMet
ValSerGluAlaAlaArgPheThrPheIle
GluAsnGlnIleArgAsnAsnPheGlnGln
ArgIleArgProAlaAsnAsnThrIleSer
LeuGluAsnLysTrpGlyLysLeuSerPhe
GlnIleArgThrSerGlyAlaAsnGlyMet
PheSerGluAlaValGluLeuGluArgAla
AsnGlyLysLysTyrTyrValThrAlaVal
AspGlnValLysProLysIleAlaLeuLeu
LysPheValAspLysAspProGlu.
4. The DNA sequence of claim 2 , further defined as having the nucleotide sequence:
GGNYTNGAYA CNGTNWSNTT YWSNACNAAR GGNGCNACNT AYATHACNTA YGTNAAYTTY
60
YTNAAYGARY TNMGNGTNAA RYTNAARCCN GARGGNAAYW SNCAYGGNAT HCCNYTNYTN
120
MGNAARGGNG AYGAYCCNGG NAARTGYTTY GTNYTNGTNG CNYTNWSNAA YGAYAAYGGN
180
CARYTNGCNG ARATHGCNAT HGAYGTNACN WSNGTNTAYG TNGTNGGNTA YCARGTNMGN
240
AAYMGNWSNT AYTTYTTYAA RGAYGCNCCN GAYGCNGCNT AYGARGGNYT NTTYAATAAY
300
ACNATHAARA AYCCNYTNYT NTTYGGNGGN AARACNMGNY TNCAYTTYGG NGGNWANTAY
360
CCNWSNYTNG ARGGNGARAA RGCNTAYMGN GARACNACNG AYYTNGGNAT HGARCCNYTN
420
MGNATHGGNA THAARAARYT NGAYGARAAY GCNATHGAYA AYTAYAARCC NACNGARATH
480
GCNWSNWSNY TNYTNGTNGT NATHCARATG GTNWSNGARG CNGCNMGNTT YACNTTYATH
540
GARAAYCARA THMGNAAYAA YTTYCARCAR MGNATHMGNC CNGCNAAYAA YACNATHWSN
600
YTNGARAAYA ARTGGGGNAA RYTNWSNTTY CARATHMGNA CNWSNGGNGC NAAYGGNATG
660
TTYWSNGARG CNGTNGARYT NGARMGNGCN AAYGGNAARA ARTAYTAYGT NACNGCNGTN
720
GAYCARGTNA ARCCNAARAT HGCNYTNYTN AARTTYGTNG AYAARGAYCC NGAR
774
wherein
R = or G
K = G or T
N = any
Y = C or T
M = A or C
S = C or G
B = C, G, or T
V = A, C, or G
W = A or T
D = A, G, or T
H = A, C, or T
X = unknown.
5. The gelonin toxin of claim 1 or claim 3 , further defined as a fusion protein that includes a functional modality in addition to said toxin.
6. The gelonin toxin of claim 5 wherein the fusion protein is prepared by conjugation of the functional modality to the toxin.
7. The gelonin toxin of claim 5 , wherein the fusion protein is prepared by recombinant technology.
8. The gelonin toxin of claim 5 , wherein said functional modality is an antibody.
9. The gelonin toxin of claim 5 , wherein the functional modality is a targeting ligand.
10. The gelonin toxin of claim 9 , wherein the targeting ligand is IL- 2 .
11. The gelonin toxin of claim 9 , wherein the targeting ligand is EGF.
12. The gelonin toxin of claim 9 , wherein the targeting ligand is IFN.
13. The gelonin toxin of claim 5 , wherein the functional modality is a second toxic activity.
14. The gelonin toxin of claim 13 , wherein said second toxic activity is diptheria toxin action.
15. The gelonin toxin of claim 5 wherein the functional modality is TNF.
16. The gelonin toxin of claim 5 , wherein the functional modality is a chemotherapeutic agent.
17. The gelonin toxin of claim 5 , wherein the functional modality is a radioisotope.
18. The gelonin toxin of claim 1 or claim 3 , further defined as lacking carbohydrate groups.Cited by (0)
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References (0)
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