View source for Chemistry:FK1012

{{Short description | Dimer for protein manipulation}}
{{Chembox
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| ImageFile = FK1012 skeletal.svg
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| IUPACName = (1''R'',12''S'',13''R'',14''S'',18''E'',21''S'',23''S'',24''R'',25''R'',27''R'')-1,14-Dihydroxy-17-<nowiki/>{(2''E'')-4-[(12''S'',13''R'',14''S'',17''R'',18''E'',21''S'',23''S'',24''R'',25''R'',27''R'')-14-hydroxy-12-<nowiki/>{(1''E'')-1-[(1''R'',3''R'',4''R'')-4-hydroxy-3-methoxycyclohexyl]-1-propen-2-yl}-23,25-dimethoxy-13,19,21,27-tetramethyl-2,3,10,16-tetraoxo-11,28-dioxa-4-azatricyclo[22.3.1.0<sup>4,9</sup>]octacos-18-en-17-yl]-2-buten-1-yl}-12-<nowiki/>{(1''E'')-1-[(1''R'',3''R'',4''R'')-4-hydroxy-3-methoxycyclohexyl]-1-propen-2-yl}-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0<sup>4,9</sup>]octacos-18-ene-2,3,10,16-tetrone
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| Section1 = {{Chembox Identifiers
| CASNo = 
| ChemSpiderID = 23193198
| PubChem = 44337639
| ChEMBL = 405628
| SMILES = C[C@@H]1C[C@@H]([C@@H]2[C@@H](C[C@H](C(O2)C(=O)C(=O)N3CCCCC3C(=O)O[C@@H]([C@@H]([C@H](CC(=O)[C@@H](/C=C(/C1)\C)C/C=C/CC4/C=C(/C[C@@H](C[C@@H]([C@@H]5[C@@H](C[C@H]([C@@](O5)(C(=O)C(=O)N6CCCCC6C(=O)O[C@@H]([C@@H]([C@H](CC4=O)O)C)/C(=C/[C@@H]7CC[C@H]([C@@H](C7)OC)O)/C)O)C)OC)OC)C)\C)O)C)/C(=C/[C@@H]8CC[C@H]([C@@H](C8)OC)O)/C)C)OC)OC
| StdInChI=1S/C86H134N2O23/c1-47-33-49(3)37-71(104-13)79-73(106-15)41-53(7)78(108-79)75(95)82(97)87-31-21-19-25-61(87)84(99)109-76(51(5)39-57-27-29-63(89)69(43-57)102-11)55(9)65(91)45-67(93)59(35-47)23-17-18-24-60-36-48(2)34-50(4)38-72(105-14)80-74(107-16)42-54(8)86(101,111-80)81(96)83(98)88-32-22-20-26-62(88)85(100)110-77(56(10)66(92)46-68(60)94)52(6)40-58-28-30-64(90)70(44-58)103-12/h17-18,35-36,39-40,49-50,53-66,69-74,76-80,89-92,101H,19-34,37-38,41-46H2,1-16H3/b18-17+,47-35+,48-36+,51-39+,52-40+/t49-,50-,53+,54+,55+,56+,57-,58-,59+,60?,61?,62?,63+,64+,65-,66-,69+,70+,71-,72-,73+,74+,76+,77+,78?,79+,80+,86+/m0/s1
| StdInChIKey = IOISFHIZCFPBTB-HSZXOJBTSA-N
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| Section2 = {{Chembox Properties
| Formula =
| C=86 | H=134 | N=2 | O=23
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| Section3 = {{Chembox Hazards
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'''FK1012''' is a [[Chemistry:Dimer|dimer]] consisting of two molecules of [[Chemistry:Tacrolimus|tacrolimus]] (FK506) linked via their [[Chemistry:Vinyl group|vinyl]] groups.<ref>{{cite journal|title=Single-step syntheses of cell permeable protein dimerizers that activate signal transduction and gene expression |author=Steven T. Diver |author2=Stuart L. Schreiber |journal=J. Am. Chem. Soc.|year=1997|volume=119|issue=22|pages=5106–5109|doi=10.1021/ja963891c}}</ref> It is used as a research tool in [[Biology:Chemically induced dimerization|chemically induced dimerization]] applications. FK1012 is a [[Biology:Chemically induced dimerization|chemical inducer of dimerization]] (CID) which makes the protein capable of dimerization or oligomerization of fusion proteins containing one or more FKBP12 domains.<ref>{{Cite journal |last=Keenan |first=Terence |last2=Yaeger |first2=David R. |last3=Courage |first3=Nancy L. |last4=Rollins |first4=Carl T. |last5=Pavone |first5=Mary Ellen |last6=Rivera |first6=Victor M. |last7=Yang |first7=Wu |last8=Guo |first8=Tao |last9=Amara |first9=Jane F. |last10=Clackson |first10=Tim |last11=Gilman |first11=Michael |last12=Holt |first12=Dennis A. |date=1998-08-01 |title=Synthesis and activity of bivalent FKBP12 ligands for the regulated dimerization of proteins |url=https://www.sciencedirect.com/science/article/pii/S0968089698001254 |journal=Bioorganic & Medicinal Chemistry |volume=6 |issue=8 |pages=1309–1335 |doi=10.1016/S0968-0896(98)00125-4 |issn=0968-0896}}</ref> It is used in pharmacology to act as a mediator in the formation of FK506 dimer.<ref>{{Cite journal |last=Blau |first=C. Anthony |last2=Peterson |first2=Kenneth R. |last3=Drachman |first3=Jonathan G. |last4=Spencer |first4=David M. |date=1997 |title=A Proliferation Switch for Genetically Modified Cells |url=https://www.jstor.org/stable/41778 |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=94 |issue=7 |pages=3076–3081 |issn=0027-8424}}</ref> [[Biology:FKBP|FK506 binding proteins]] (FKBPs) do not normally form dimers but can be caused to dimerize in the presence of FK1012. Genetically engineered proteins based on FKBPs can be used to manipulate protein localization, signaling pathways and protein activation.<ref>{{cite journal|last=Fegan|first=A|author2=White, B |author3=Carlson, JC |author4= Wagner, CR |title=Chemically controlled protein assembly: techniques and applications.|journal=Chemical Reviews|date=Jun 9, 2010|volume=110|issue=6|pages=3315–36|pmid=20353181|doi=10.1021/cr8002888}}</ref>

==References==
{{reflist}}

==Further reading==
* {{cite journal|title=Cell proliferation through forced engagement of c-Kit and Flt-3|journal=Blood|volume=97|issue=11|pages=3662–4|doi=10.1182/blood.V97.11.3662|pmid=11369667|year=2001|last1=Otto|first1=K. G.|last2=Jin|first2=L|last3=Spencer|first3=D. M.|last4=Blau|first4=C. A.|doi-access=free}}

[[Category:Macrolides]]
[[Category:Dimers (chemistry)]]



{{Sourceattribution|FK1012}}