P R O D UC T FLYER

The PARP Family& ADP Ribosylation
TTomorrow’s Reagents Manufactured Today®

International Edition

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The PARP Family

Latest Insight
Picture courtesy of J.C. Amé, V. Schreiber & G. de Murcia (CNRS, Strasbourg)

NEW PARP Isoform SpecificInhibitors see Page 6

Third Zinc-binding Domain of
PARP-1PARP-1 contains three major segments that represent the biochemical activities of the enzyme: theDNA-binding domain (DBD), the automodification
domain, and the catalytic domain. Recently, M.F. Langelier, et al. identified a third zinc finger domain in
the DBD of human PARP-1. This domain mediates interdomain contacts important for DNA-dependent
enzyme activation.
LIT: A third zinc-binding domain of human poly(ADP-ribose) polymerase-1
coordinates DNA-dependent enzyme activation: M.F. Langelier, et al.; J. Biol.
Chem. 283, 4105 (2008)

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TH E PA RP FA MI LY

International Edition

2

The PARP Family
Introduction
Poly(ADP-ribosyl)ation is a post-translational
modification process which plays a critical rolein diverse cellular functions such as DNA damage detection and repair, transcriptional regulation, intracellular trafficking, chromatin modification, mitotic apparatus formation, and cell
death. The process is mediated by membersof the family of poly(ADP-ribose) polymerases (PARPs), which transfer ADP-ribose (ADPr)
units from nicotinamide dinucleotide (NAD)to certain residues in PARPs and onto target
proteins. PARPs also mediate the polymerization of ADP-riboses via glycosidic bonds, creating long and branched ADP-ribose polymers,
which are subsequently degraded by polyADPribose glycohydrolase (PARG). ADP-ribose polymers are thought to modify protein functions.
In humans, the PARP family members are encoded by 17 different genes, while PARP-1 isthe founding member [1-3].

FIGURE: PARP-1, PARP-2, NAD and CarbaNAD in complex.
Picture courtesy of J.C. Amé & V. Schreiber (CNRS, Strasbourg)

DNA Repair (Cell Survival)

DNA-independent Activation

PARP-1 has been implicated in multiple DNA
repair pathways including single-strand breakrepair (SSBR), double strand break (DSB) repair
and base excision repair (BER). The molecularmechanism of BER may involve a local chromatin relaxation mediated either by covalentmodification of histones with poly(ADP-ribose)or by non-covalent interaction of histones withpoly(ADP-ribose) that automodifies the enzyme. This might regulate the accessibility toother DNA repair proteins. In addition PARP-1
or poly(ADP-ribose) (PAR) may directly recruit
repair proteins like XRCC1 (X-ray repair crosscomplementing 1) to the site of DNA damage[4-7]. PARP-2 is the only other known member of the PARP family to be activated by DNA
strand breaks [8]. Although its DNA-binding domain is different from that of PARP-1, PARP-2
has been shown to interact with the SSBR/BER
repair factors XRCC1, DNA polymerase β andDNA ligase III [9]. PARP-2 seems to be involvedin later steps of the repair processes [10]. Beside
its role in DNA repair, PARP-2 has been shown to
be involved in diverse processes such as spermatogenesis, adipogenesis and T cell development [11].
BRCA1 and BRCA2 are tumor suppressor proteins important for DSB repair by homologous recombination. For a review see [12]. It
has been demonstrated that BRCA1 or BRCA2
deficient cells have lost their ability to repair
single-strand breaks by homologous recombination (HR) after PARP-1 depletion or inhibition, which can result in cell cycle arrest andapoptosis [13, 14]. This specific killing of tumor
cells led to PARP inhibitors entering clinical trials and the screen for genes mediating such lethal sensitivity [15, 16]. Interestingly, two recent
studies showed that antitumor chemotherapy
with platinum analogs and PARP inhibitors can
induce counter-mutation restoring HR capabilities of BRCA2 deficient cells [17, 18].

Recent findings revealed that PARP-1 can be activated by a DNA independent mode [19, 20].
This alternative mechanism is mediated byphosphorylated ERK2, showing that PARP-1
plays a role in the ERK signalling cascade mediating growth and differentiation. Activated
PARP-1 increased ERK2-catalyzed Elk1 phosphorylation, histone acetylation, and the expression of the Elk1-targeted gene c-Fos [19].

Apoptosis / Necrosis (Cell Death)
Whereas activation of PARP-1 by mild genotoxic
stimuli may facilitate DNA repair and cell survival, massive DNA damage may trigger hyperactivation of PARP-1 and cell death [21]. Excessive PARP-1 activity and PAR synthesis have beenshown to induce cell death by causing NAD+/ATP depletion [22-23] as well as triggering therelease and nuclear translocation of apoptosis
inducing factor [24, 25]. AIF induced cell deathin response to the alkylating agent N-methylN’-nitro-N’-nitrosoguanidine (MNNG) requires
calpains and Bax next to PARP-1 [26]. Recent results indicate a direct toxicity of PAR itself causing cellular death independent of energetic ortranscriptional changes [27, 28]. PARP-1 activation is thought to be a key mediator of neuronal death during excitotoxicity, ischemia, andoxidative stress, as well as being of importancefor other neuronal diseases [29-30].

PARP and Transcription
PARP-1 may regulate transcription by at least
two different mechanisms. It can act as a modulator of the chromatin structure, but also functions as a component of enhancer/promoter
regulatory complexes. PARP-1 can interact withthe enhancers and promoters of genes by a)direct sequence-specific binding to enhancers, b) recruitment via DNA binding transcription factors (e.g. NF-κB), and c) direct binding
to DNA structures.

LIT: [1] Poly(ADP-ribose): novel functions for an old molecule: V.
Schreiber, et al.; Nat. Rev. Mol. Cell Biol. 7, 517 (2006)  [2] cDNA sequence, protein structure, and chromosomal location of the humangene for poly(ADP-ribose) polymerase: B. W. Cherney, et al.; PNAS 84,
8370 (1987)  [3] Human nuclear NAD+ ADP-ribosyltransferase: localization of the gene on chromosome 1q41-q42 and expression ofan active human enzyme in Escherichia coli: H. Herzog, et al.; PNAS
86, 3514 (1989)  [4] XRCC1 is specifically associated with poly(ADPribose) polymerase and negatively regulates its activity following
DNA damage: M. Masson, et al.; Mol. Cell Biol. 18, 3563 (1998)  [5]Poly(ADP-ribose) binds to specific domains in DNA damage checkpoint proteins: J. M. Pleschke, et al.; J. Biol. Chem. 275, 40974 (2000)
 [6] A requirement for PARP-1 for the assembly or stability of XRCC1
nuclear foci at sites of oxidative DNA damage: S. F. El-Khamisy, et al.;Nucleic Acids Res. 31, 5526 (2003)  [7] The role of poly(ADP-ribose)in the DNA damage signaling network: M. Malanga & F. R. Althaus;
Biochem. Cell Biol. 83, 354 (2005)  [8] PARP-2, a novel mammalian
DNA damage-dependent poly(ADP-ribose) polymerase: J. C. Ame, etal.; J. Biol. Chem. 274, 17860 (1999)  [9] Poly(ADP-ribose) polymerase-2 (PARP-2) is required for efficient base excision DNA repair in
association with PARP-1 and XRCC1: V. Schreiber, et al.; J. Biol. Chem.
277, 23028 (2002)  [10] Feedback-regulated poly(ADP-ribosyl)ation
by PARP-1 is required for rapid response to DNA damage in living
cells: O. Mortusewicz, et al.; Nucleic Acids Res. 35, 7665 (2007)  [11]Toward specific functions of poly(ADP-ribose) polymerase-2: J. Yelamos, et al.; Trends Mol. Med. 14, 169 (2008)  [12] Role of BRCA1and BRCA2 as regulators of DNA repair, transcription, and cell cycle in response to DNA damage: K. Yoshida & Y. Miki; Cancer Sci. 95,
866 (2004)  [13] Specific killing of BRCA2-deficient tumours with
inhibitors of poly(ADP-ribose) polymerase: H. E. Bryant, et al.; Nature 434, 913 (2005)  [14] Targeting the DNA repair defect in BRCA
mutant cells as a therapeutic strategy: H. Farmer, et al.; Nature 434,
917 (2005)  [15] Clinical poly(ADP-ribose) polymerase inhibitors forthe treatment of cancer: C. Lewis & J. A. Low; Curr. Opin. Investig.
Drugs 8, 1051 (2007)  [16] A synthetic lethal siRNA screen identifying genes mediating sensitivity to a PARP inhibitor: N. C. Turner, etal.; EMBO J., Epub ahead of print, (2008)  [17] Secondary mutations
as a mechanism of cisplatin resistance in BRCA2-mutated cancers:
W. Sakai, et al.; Nature 451, 1116 (2008)  [18] Resistance to therapy
caused by intragenic deletion in BRCA2: S. L. Edwards, et al.; Nature
451, 1111 (2008)  [19] DNA-independent PARP-1 activation by phosphorylated ERK2 increases Elk1 activity: a link to histone acetylation:
M. Cohen-Armon, et al.; Mol. Cell 25, 297 (2007)  [20] PARP-1 activation in the ERK signaling pathway: M. Cohen-Armon; TIPS 28, 556(2007)  [21] Poly(ADP-ribose) makes a date with death: J. T. Heeres& P. J. Hergenrother; Curr. Opin. Chem. Biol. 11, 644 (2007)  [22]Poly(ADP-ribose) polymerase is a mediator of necrotic cell death by
ATP depletion: H. C. Ha & S. H. Snyder; PNAS 96, 13978 (1999)  [23]Alkylating DNA damage stimulates a regulated form of necrotic cell
death: W. X. Zong, et al.; Genes Dev. 18, 1272 (2004)  [24] Mediationof poly(ADP-ribose) polymerase-1-dependent cell death by apoptosis-inducing factor: S. W. Yu, et al.; Science 297, 259 (2002)  [25]Apoptosis-inducing factor mediates poly(ADP-ribose) (PAR) polymerinduced cell death: S. W. Yu, et al.; PNAS 103, 18314 (2006)  [26] Sequential activation of poly(ADP-ribose) polymerase 1, calpains, andBax is essential in apoptosis-inducing factor-mediated programmed
necrosis: R. S. Moubarak, et al.; Mol. Cell Biol. 27, 4844 (2007)  [27]Poly(ADP-ribose) (PAR) polymer is a death signal: S. A. Andrabi, et al.;PNAS 103, 18308 (2006)  [28] Neither energy collapse nor transcription underlie in vitro neurotoxicity of poly(ADP-ribose) polymerase
hyper-activation: S. Fossati, et al.; Neurochem. Int. 50, 203 (2007) [29] The role of poly(ADP-ribose) polymerase-1 in CNS disease: T. M.
Kauppinen & R. A. Swanson; Neuroscience 145, 1267 (2007)  [30]Multiple roles for poly(ADP-ribose)polymerase-1 in neurological disease: T. M. Kauppinen; Neurochem. Int. 50, 954 (2007)

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PARP Proteins
Standard PARP Proteins

PARP Family Proteins & Related Products
Product

SourcePurityProd. No.

Size

PARP-1 (human) (rec.) (His)

Produced in Sf21 cells≥98%

ALX-201-250-C010

10 μg

PARP-1 (Cat. Dom.) (human) (rec.) (His)

Produced in Sf21 cells>90 %ALX-201-232-C020

20 μg

PARP-1 (BRCT Domain) (human) (rec.) (His)

Produced in E. coli≥98%

ALX-201-255-C020

20 μg

PARP-1 (E988K mutant) (human) (rec.)Produced in Sf21 cells≥95 %ALX-201-254-C010

10 μg

PARP-1b (human) (rec.) (active) (His)

Produced in Sf21 cells≥95%

ALX-201-253-C020

20 μg

PARP-1 (bovine)

Isolated from calf thymus~90%

ALX-202-042-C010

10 μg

PARP-1 (bovine)

Isolated from calf thymus~98%

ALX-202-046-C010

10 μg

PARP-1 (bovine) (automod.) Standard

Isolated from calf thymus

ALX-202-044-R100

100 μlPARP-2 (mouse) (rec.) (high purity)

PARP-2 (mouse) (rec.) (His)

Produced in Sf21 cells≥98%

ALX-201-251-C010

10 μg[Poly(ADP-ribose) Polymerase-2 (mouse) (rec.)]

PARP-3 (human) (rec.) (His)

Produced in Sf21 cells≥98%

ALX-201-252-C010

10 μg

ALX-201-064-C020
Produced in Sf9 cells.

Poly(ADP-ribose) [PAR] Standard

Automodified PARP-1≥95%

ALX-202-043-C001

1 μg

PARG (bovine)

Isolated from calf thymus

ALX-202-045-UC01

0.1 U

PARP-1 (human) (rec.) (high purity)[Poly(ADP-ribose) Polymerase-1 (human) (rec.)]

ALX-201-063-C020
Produced in Sf9 cells.

20 μg

LIT: Overproduction and large-scale purification of the humanpoly(ADP- ribose) polymerase using a baculovirus expression system: H. Giner, et al.; Gene 114, 279 (1992)  Poly(ADPribose) reactivates stalled DNA topoisomerase I and Induces
DNA strand break resealing: M. Malanga & F.R. Althaus; J. Biol.
Chem. 279, 5244 (2004)

20 μg

LIT: PARP-2, A novel mammalian DNA damage-dependentpoly(ADP-ribose) polymerase: J.C. Ame, et al.; J. Biol. Chem.
274, 17860 (1999)  A bidirectional promoter connects thepoly(ADP-ribose) polymerase 2 (PARP-2) gene to the gene for
RNase P RNA. structure and expression of the mouse PARP-2
gene: J.C. Ame, et al.; J. Biol. Chem. 276, 11092 (2001)  Poly(ADPribose) reactivates stalled DNA topoisomerase I and Induces
DNA strand break resealing: M. Malanga & F.R. Althaus; J. Biol.
Chem. 279, 5244 (2004)

PARP-3 (human) (rec.) (high purity)[Poly(ADP-ribose) Polymerase-3 (human) (rec.)]

ALX-201-170-C020
Produced in Sf9 cells.

20 μg

LIT: PARP-3 localizes preferentially to the daughter centriole andinterferes with the G1/S cell cycle progression: A. Augustin, etal.; J. Cell Sci. 116, 1551 (2003)  Tankyrase-1 polymerization ofpoly(ADP-ribose) is required for spindle structure and function:
P. Chang et al.; Nature Cell Biology 7, 1133 (2005)

TH E PA RP FA MI LY

International Edition

VPARP (PARP-4)
Vault poly(ADP-ribose) polymerase (VPARP;
PARP-4) was originally identified as a minor
protein component of the vault ribonucleoprotein particle [1]. Vaults have been implicated in
multidrug resistance of human tumors and arethought to be involved in macromolecular assembly and/or transport [2]. In addition to theassociation of VPARP with the cytoplasmic vault
particle, subpopulations of VPARP localize tothe nucleus and the mitotic spindle, indicatingthat VPARP may have other cellular functions.
Recently, VPARP has been shown to associatewith telomerase activity and interact with exogenously expressed telomerase-associated protein 1 (TEP1) in mammalian cells [3].

LIT: [1] The 193-kD vault protein, VPARP, is a novel poly(ADP-ribose)polymerase: V.A. Kickhoefer, et al.; J. Cell Biol. 146, 917 (1999)  [2]Cellular functions of vaults and their involvement in multidrug resistance: E. Steiner, et al.; Curr. Drug Targets 7, 923 (2006)  [3] Vault
poly(ADP-ribose) polymerase is associated with mammalian telomerase and is dispensable for telomerase function and vault structure
in vivo: Y. Liu, et al.; Mol. Cell. Biol. 24, 5314 (2004)

VPARP (human) (rec.) (His)[Minor Vault p193 Protein (human) (rec.) (His); PARP-4(human) (rec.) (His)]

ALX-201-286-C010
Produced in E. coli.

10 μg

LIT: In silico characterization of the family of PARP-like poly(ADPribosyl)transferases (pARTs): H. Otto, et al.; BMC Genomics 6, 139(2005)XRCC1
Human XRCC1 (X-ray repair cross-complementing 1) is involved in base excision repair(BER) and single strand break repair (SSBR) andthought to act as a scaffolding protein for otherrepair factors. It has been shown to physically interact with several enzymes known to be
involved in the repair of SSBs, including DNA
ligase IIIα, DNA polymerase β, APE1, poly- [3] Role of XRCC1 in the coordination and stimulation of oxidative DNA damage repair initiated by the DNA glycosylase hOGG1: S.
Marsin, et al.; J. Biol. Chem. 278, 44068 (2003)  [4] XRCC1 stimulates
human polynucleotide kinase activity at damaged DNA termini andaccelerates DNA single-strand break repair: C. J. Whitehouse, et al.;Cell 104, 107 (2001)  [5] Poly(ADP-ribose) polymerase-2 (PARP-2)
is required for efficient base excision DNA repair in association with
PARP-1 and XRCC1: V. Schreiber, et al.; J. Biol. Chem. 277, 23028 (2002)
 [6] Spatial and temporal cellular responses to single-strand breaks
in human cells: S. Okano, et al.; Mol. Cell. Biol. 23, 3974 (2003)

nucleotide kinase/phosphatase, poly(ADPribose) polymerases 1 and 2 (PARP-1 and 2) and
8-oxoguanine DNA glycosylase (OGG1) [1-6].
LIT: [1] XRCC1 polypeptide interacts with DNA polymerase beta andpossibly poly (ADP-ribose) polymerase, and DNA ligase III is a novel
molecular ‚nick-sensor‘ in vitro: K. W. Caldecott, et al.; Nucleic Acids
Res. 24, 4387 (1996)  [2] Reconstitution of DNA base excision-repair
with purified human proteins: interaction between DNA polymerase
beta and the XRCC1 protein: Y. Kubota, et al.; EMBO J. 15, 6662 (1996)

Product

Source / Host

Specificity

Application

Prod. No.

Size

PAb to XRCC1 (human)

From rabbit

Human

ELISA, ICC, IP, WB

ALX-210-304-R050

50 μl

PAb to XRCC1 (human)

From rabbit

Human

ICC, IP, WB

ALX-210-539-R100

100 μl

PAb to XRCC1 (human) (exon 17)

From rabbit

Human

ICC, IHC, IP, WB

BET-A300-065A

0.1 mg

PAb to XRCC1 (human) (phosphorylated) (pSer461)

From rabbit

Human

WB

BET-A300-147A

0.1 mg

PAb to XRCC1 (human) (phosphorylated) (pSer475)

From rabbit

Human

WB

BET-A300-227A

0.1 mg

PAb to XRCC1 (human) (phosphorylated) (pSer485/pThr488)

From rabbit

Human

WB

BET-A300-231A

0.1 mg

PAb to XRCC1 (human) (phosphorylated) (pSer518/pThr519/pThr523)

From rabbit

Human

WB

BET-A300-059A

0.1 mg

PAb to XRCC1 (phosphorylated) (pSer461)

From rabbit

Human, mouse

IHC (PS)

BET-IHC-00116

0.1 ml

PAb to XRCC1 (phosphorylated) (pSer485/pThr488)

From rabbit

Human, mouse

IHC (PS)

BET-IHC-00117

0.1 ml

PAb to XRCC1 (phosphorylated) (pSer518/pThr519/pThr523)

From rabbit

Human, mouse

IHC (PS)

BET-IHC-00115

0.1 mlPurified (PF) = Purified (Preservative free); FC = Flow Cytometry; ICC = Immunocytochemistry; IP = Immunoprecipitation;
IHC = Immunohistochemistry (FS = Frozen Sections, PS = Paraffin Sections); WB = Western blot; BP = Blocking Peptide3

TH E PA RP FA MI LY

International Edition

PARP Antibodies
Standard Antibodies
MAb to Poly(ADP-ribose) (10H)

MAb to PARP-1 (C2-10)

MAb to VPARP (human) (p193-4)

ALX-804-220-R100
100 μl
CLONE: 10H. ISOTYPE: Mouse IgG3. IMMUNOGEN:
Purified poly(ADP-ribose). SPECIFICITY: Recognizes poly(ADP-ribose) synthesized bya broad range of PARPs (poly(ADP-ribose)polymerases) like human, mouse, rat or Drosophila PARP enzyme. APPLICATION: FC, IHC(PS), ICC, WB.

ALX-804-210-R050
50 μl
CLONE: C2-10. ISOTYPE: Mouse IgG1. IMMUNO
GEN: Purified calf thymus PARP-1 (poly(ADPribose) polymerase-1). SPECIFICITY: Recognizes an epitope in the C-terminal part of the
DNA binding domain of human, mouse, rat,
hamster and primate PARP-1. Detects bands~116kDa (intact PARP-1) and ~85kDa (apoptosis-induced cleavage fragment) by Westernblot. APPLICATION: ELISA, ICC, IP, WB.

ALX-801-023-C125
125 μg
ALX-801-023-C250
250 μg
CLONE: p193-4. ISOTYPE: Mouse IgG1. IMMUNOGEN:
VPARP (minor vault p193 protein; PARP-4).
SPECIFICITY: Recognizes epitope aa 491-494 ofhuman VPARP. APPLICATION: IHC (FS, PS), ICC,
IP, WB.

LIT: Monoclonal antibodies to poly(adenosine diphosphate ribose)recognize different structures: H. Kawamitsu, et al.; Biochemistry23, 3771 (1984) (Original Reference)  For a comprehensive bibliography please visit our website.

FOR MORE INFORMATION SEE BACKCOVER

PAb to Poly(ADP-ribose) (96-10-04)
ALX-210-890-R100
100 μlFrom rabbit. IMMUNOGEN: Poly(ADP-ribose)with methylated BSA. SPECIFICITY: Recognizes poly(ADP-ribose) of 6-100 bases in size,
synthesized in vitro or in vivo. Shows somecross-reactivity with BSA. APPLICATION: ELISA,
ICC, WB.
LIT: Failure to degrade poly(ADP-ribose) causes increased sensitivity to cytotoxicity and early embryonic lethality: D.W. Koh, etal.; PNAS 101, 17699 (2004)  Ataxia telangiectasia mutated (ATM)signaling network is modulated by a novel poly(ADP-ribose)-dependent pathway in the early response to DNA-damaging agents:
J.F. Haince, et al.; J. Biol. Chem. 282, 16441 (2007)  For a comprehensive bibliography please visit our website.

LIT: Structural and functional analysis of poly(ADP ribose) polymerase: an immunological study: D. Lamarre, et al.; Biochim. Biophys.
Acta 950, 147 (1988)  Cleavage of poly(ADP-ribose) polymerase
by a proteinase with properties like ICE: Y.A. Lazebnik, et al.; Nature
371, 346 (1994)  Nuclear poly(ADP-ribose) polymerase-1 rapidly
triggers mitochondrial dysfunction: G. Cipriani, et al.; J. Biol. Chem.
280, 17227 (2005)  For a comprehensive bibliography please
visit our website.

MAb to PARP-2 (4G8)
ALX-804-639-L001
1 ml
CLONE: 4G8. ISOTYPE: Mouse IgG1. IMMUNOGEN:
Recombinant mouse PARP-2 (poly(ADP-ribose) polymerase-2). SPECIFICITY: Recognizes
an epitope in domain E of human and mouse
PARP-2. Detects a band of ~62kDa by Westernblot. APPLICATION: ELISA, WB.

LIT: The Mr 193,000 vault protein is up-regulated in multidrugresistant cancer cell lines: A.B. Schroeijers, et al.; Cancer Res. 60,
1104 (2000)  The formation of vault-tubes: a dynamic interaction between vaults and vault PARP: A. Van Zon, et al.; J. Cell Sci.
116, 4391 (2003)  For a comprehensive bibliography please visit
our website.

MAb to Tankyrase-1 (human) (19A449)
ALX-804-234-C100
100 μg
CLONE: 19A449. ISOTYPE: Mouse IgG1. IMMUNOGEN: Recombinant human tankyrase-1(PARP-5a). SPECIFICITY: Recognizes humantankyrase-1. Detects a band of ~120kDa byWestern blot. APPLICATION: WB.
LIT: Tankyrase, a poly(ADP-ribose) polymerase at human telomeres:
S. Smith, et al.; Science 282, 1484 (1998)  Mammalian telomeresend in a large duplex loop: J.D. Griffith, et al.; Cell 97, 503 (1999) Tankyrase is a golgi-associated mitogen-activated protein kinase
substrate that interacts with IRAP in GLUT4 vesicles: N.W. Chi & H.F.
Lodish; J. Biol. Chem. 275, 38437 (2000)  For a comprehensive
bibliography please visit our website.

LIT: Anti-Poly-ADP-Ribose Polymerase-2 (PARP-2) Mouse MAb 4G8:
Y. Monreal, et al.; Hybridoma 25, 102 (2006)

PARP Family Antibodies & Related Products

4

Product

Source / Host / Isotype

Specificity

Application

Prod. No.

MAb to Poly(ADP-ribose) [PAR] (10H)

Mouse IgG3

Human, mouse, rat

FC, ICC, IHC (PS), WB

ALX-804-220-R100

100 μlSize

PAb to Poly(ADP-ribose) [PAR]Ab: 96-10-04 / From rabbit

Human, mouse, rat

ELISA, ICC, WB

ALX-210-890-R100

100 μl

MAb to PARP-1 (C2-10)

Mouse IgG1

Human, mouse, rat, primate

ELISA, ICC, IP, WB

ALX-804-210-R050

50 μl

MAb to PARP-1 (F1-23)

Mouse IgG1

Human, bovine

ELISA, ICC, IP, WB, FUNC

ALX-804-211-R050

50 μl

PAb to PARP-1

From rabbit

Human, mouse, bovine, chicken

ELISA, ICC, IHC (FS, PS)

ALX-210-302-R100

100 μl

PAb to PARP-1

From rabbit

Human, mouse, rat, monkey, bovine

ICC, IP, WB, FUNC

ALX-210-221-R100

100 μl

PAb to PARP-1 (human)

From goat (serum)

Human, mouse

WB

ALX-210-897-R100

100 μl

PAb to PARP-1 (human)

From rabbit (supernatant)

Human, mouse (weak)

ICC, IHC, IP, WB

ALX-210-895-R100

100 μl

PAb to PARP-1 (mouse)

From rabbit (supernatant)

Mouse, human (weak)

ICC, IHC, IP, WB

ALX-210-619-R100

100 μl

PAb to PARP-1 (BRCT Domain)

From rabbit

Human, mouse

IP, WB

ALX-210-540-R100

100 μl

PAb to PARP-1 (197-214)

From rabbit

Human, bovine, chicken

ELISA, ICC, IP, WB

ALX-210-219-R100

100 μl

PAb to PARP-1 (215-228)

From rabbit

Human, bovine, chicken

ELISA, ICC, WB

ALX-210-220-R100

100 μl

PAb to PARP-1 (509-524)

From rabbit

Human, mouse, rat, bovine

ELISA, IP, WB, FUNC

ALX-210-222-R100

100 μl

MAb to PARP-2 (4G8)

Mouse IgG1

Human, mouse

ELISA, WB

ALX-804-639-L001

1 ml

PAb to PARP-2

Ab: Yuc / From rabbit

Human, mouse, monkey

ELISA, ICC, IP, WB

ALX-210-303-R100

100 μl

PAb to PARP-2

Ab: Yuc / From rabbit, purified

Human, mouse, monkey

ICC

ALX-210-896-R100

100 μl

PAb to PARP-2 (mouse)

From rabbit (supernatant)

Mouse, human (weak)

ICC, IHC, IP, WB

ALX-210-899-R100

100 μl

MAb to PARP-3 (LA6B10)

Mouse IgM

Human, mouse

ICC

ALX-804-466-R100

100 μl

PAb to PARP-3

From rabbit

Human, mouse, monkey

ICC, IP, WB

ALX-210-541-R100

100 μl

MAb to VPARP/PARP-4 (p193-4)

Mouse IgG1

Human

ICC, IHC (FS, PS), IP, WB

ALX-801-023-C125

125 μg

MAb to VPARP/PARP-4 (p193-6)

Mouse IgG2b

Human

ICC, IHC (FS), WB

ALX-801-024-C125

125 μg

MAb to VPARP/PARP-4 (p193-10)

Mouse IgG2a

Human

IHC, WB

ALX-801-025-C125

125 μg

MAb to Tankyrase-1 [PARP-5a] (19A449)

Mouse IgG

Human, mouse

WB

ALX-804-234-C100

100 μg

MAb to PARP-10 (human) (5H11)

Rat IgG1

Human

ICC, IP, WB

ALX-804-626-L001

1 ml

PAb to PARP-10 (300-350) (human)

From rabbit

HumanIP, WB

BET-A300-665A

0.1 mg

PAb to PARP-16 (human)

From rabbit

Human

WB

ASB-ARP33751-P050

50 μg

PAb to PARN (mouse)

From rabbit

Mouse

WB

ASB-ARP37393-T100

100 μgFor updated prices and additional information visit www.alexis-biochemicals.com, contact your local distributor, or call +41 61 926 89 89.

TH E PA RP FA MI LY

International Edition

PARP-3P
PAb to PARP-3
ALX-210-541-R100
100 μlFrom rabbit. IMMUNOGEN: Recombinant human PARP-3 (poly(ADP-ribose) polymerase-3). SPECIFICITY: Recognizes human,
mouse and monkey PARP-3. APPLICATION:
ICC, IP, WB.
LIT: PARP-3 localizes preferentially to the daughter centriole andinterferes with the G1/S cell cycle progression: A. Augustin, etal.; J. Cell Sci. 116, 1551 (2003)

H
Human
PARP-3 (hPARP-3) (540aa, with anaapprox. mass of 67kDa) is a core componentof the centrosome and preferentially localo
ized to the daughter centriole throughoutiz
the cell cycle. The N-terminal domain (54aa)
of hPARP-3 is responsible for its centrosomal
localization.
An attractive hypothesis is that the presenceof both PARP-1 and PARP-3 at the centrosome
may link the DNA damage surveillance network to the mitotic fidelity checkpoint.
LIT: PARP-3 localizes preferentially to the daughter centriole and interferes with the G1/S cell cycle progression: A. Augustin, et al.; J.
Cell Sci. 116, 1551 (2003)

MAb to PARP-3 (LA6B10)

FIGURE: Immunodetection of PARP-3 in mouse embryonic
fibroblasts fixed with 2% Formaldehyde-0.1% Triton. Dilution:
1/200.

ALX-804-466-R100
100 μl
CLONE: LA6B10. ISOTYPE: Mouse IgM. IMMUNOGEN:
Synthetic peptide corresponding to N-terminal aa 8-22 (M8APKPKPWVQTEGPE22) of human
PARP-3 (poly(ADP-ribose) polymerase-3). SPE
CIFICITY: Recognizes human and mouse PARP-3.
APPLICATION: ICC.
LIT: PARP-3 localizes preferentially to the daughter centriole and interferes with the G1/S cell cycle progression: A. Augustin, et al.; J.
Cell Sci. 116, 1551 (2003)  Tankyrase-1 polymerization of poly(ADPribose) is required for spindle structure and function: P. Chang, et al.;Nat. Cell Biol. 7, 1133 (2005)

FIGURE: PARP-3 (red) preferentially localizes to the daughter centriole. The mother centriole (green) is immunostainedwith anti-acetylated α-tubulin in 3T3 cells. Picture courtesy of
C. Spenlehauer & G. de Murcia (CNRS, Strasbourg).

PARP-10

FIGURE: Immunoprecipitation. Cell lysates prepared from
COS-1 cells were immunoprecipitated with the anti-PARP-3
antibody (lane 3) or with a control antibody (lane 2). Lane 1:
input 1:15. Lane 4: purified recombinant human poly(ADPribose) polymerase-3.

FIGURE: Western blot analysis. Mouse embryonic fibroblasts(MEF), simian COS-1 cells (COS), purified recombinant humanpoly(ADP-ribose) polymerase-3.

Latest Insight
Review on PARP-2
The catalytic activity of PARP-1 and PARP-2
has been shown to be induced by DNAstrand breaks, indicating that both enzymes play a role in the cellular response
to DNA damage. J. Yelamos, et al. reviewed
recent data that suggest unique functions
for PARP-2 in specific biological processes
such as adipogenesis, genome surveillance,
spermatogenesis and T cell development.
LIT: Toward specific functions of poly(ADP-ribose) polymerase-2:
J. Yelamos, et al.; Trends Mol. Med. 14, 169 (2008) (Review)

M. Yu, et al. [1] identified and characterized anovel 150kDa protein, designated PARP-10.
PARP-10 can associate with the oncoprotein
c-Myc and possesses PARP activity, capable of poly (ADP-ribosyl)ating itself and core
histones but neither Myc nor Max. PARP-10
shuttles between the nuclear and cytoplasmic compartments that is controlled at leastin part by a leucine-rich nuclear export sequence. Functionally PARP-10 inhibits transformation of primary cells (rat embryo fibroblasts). PARP-10 might play a role in the control of cell proliferation. To regulate its target
genes, c-Myc recruits several different cofactors. K. Lesniewicz, et al. [2] suggest that
PARP-10 may function as an additional cofactor that is recruited by c-Myc. H.Y. Chou, et al.
[3] suggested that cell cycle-dependent phosphorylation of PARP-10 by CDK2 plays crucial
functions in cell proliferation.
LIT: [1] PARP-10, a novel Myc-interacting protein with poly(ADP-ribose) polymerase activity, inhibits transformation: M. Yu, et al.; Oncogene 24, 1982 (2005)  [2] Overlap of the gene encoding thenovel poly(ADP-ribose) polymerase Parp10 with the plectin 1 geneand common use of exon sequences: K. Lesniewicz, et al.; Genomics
86, 38 (2005)  [3] CDK-dependent activation of poly(ADP-ribose)polymerase member 10 (PARP10): H.Y. Chou, et al.; J. Biol. Chem.
281, 15201 (2006)

MAb to PARP-10 (human) (5H11)

ALX-804-626-L001
1 ml
CLONE: 5H11. ISOTYPE: Rat IgG1. IMMUNOGEN: Recombinant human PARP-10 (poly(ADP-ribose)polymerase-10) (aa 1-907). SPECIFICITY: Recognizes human PARP-10. APPLICATION: ICC, IP, WB.
LIT: PARP-10, a novel Myc-interacting protein with poly(ADP-ribose)polymerase activity, inhibits transformation: M. Yu, et al.; Oncogene
24, 1982 (2005)

FIGURE: Catalytic domain of PARP-10: Picture courtesy of B. Lüscher(University Aachen)c-Myc
The proto-oncogene c-Myc is implicatedin various physiological processes, like cell
growth, proliferation, loss of differentiationand cell death. It also has been implicated in
the loss of dysfunction of insulin-producing
beta cells in diabetes. Recent studies in micesuggest that c-Myc has unexpected functions
during both self-renewal and the differentiation of stem and early progenitor cells. In aneffort to identify novel c-Myc-interacting proteins, M. Yu, et al. (Oncogene 24, 1982 (2005))
recently discovered that PARP-10 can associate with the oncoprotein c-Myc.

Purified (PF) = Purified (Preservative free); FC = Flow Cytometry; ICC = Immunocytochemistry; IP = Immunoprecipitation;
IHC = Immunohistochemistry (FS = Frozen Sections, PS = Paraffin Sections); WB = Western blot; BP = Blocking Peptide

MAb to c-Myc (human) (4H3)
ALX-804-627-L001
1 ml
CLONE: 4H3. ISOTYPE: Rat IgG2a. IMMUNOGEN: Recombinant human c-Myc (aa 1-262). SPECIFICITY:
Recognizes human and zebrafish c-Myc. APPLICATION: ICC, IP, WB.

MAb to c-Myc (human) (6A10)
ALX-804-632-L001
1 ml
CLONE: 6A10. ISOTYPE: Rat IgG2a. IMMUNOGEN:
Human c-Myc (aa 1-262). SPECIFICITY: Recognizes human c-Myc. APPLICATION: ICC, IP, WB.

5

TH E PA RP FA MI LY

International Edition

The Widest Panel of PARP Inhibitors
PARP Inhibitors
ABT-888
ALX-270-444-M001
1 mg
ALX-270-444-M005
5 mg
Potent inhibitor of PARP-1
P 1 and PARP
PARP-22 (po(potency ≤5nM in vitro). Suitable for in vivo
studies. Has excellent bioavailability andgood blood-brain permeation. Increases
tumor growth delay resulting from radiation and DNA-damaging agents.
LIT: Inhibition of poly(ADP-ribose) polymerase enhances cell
death and improves tumor growth delay in irradiated lung cancer models: J.M. Albert, et al.; Clin. Cancer Res. 13, 3033 (2007)
 ABT-888, an orally active poly(ADP-ribose) polymerase inhibitor that potentiates DNA-damaging agents in preclinical tumor
models: C.K. Donawho, et al.; Clin. Cancer Res. 13, 2728 (2007)

5-AIQ . HCl[5-Aminoisoquinolinone . HCl]

ALX-270-285-M001
1 mg
ALX-270-285-M005
5 mg
Water-soluble, potent inhibitor of poly(ADPribose) polymerase-1 (PARP-1).
LIT: Effects of 5-aminoisoquinolinone, a water-soluble, potent inhibitor of the activity of poly (ADP-ribose) polymerase on the organ injury and dysfunction caused by haemorrhagic shock: M.C. McDonald, et al.; Br. J. Pharmacol. 130, 843 (2000)  For a comprehensive
bibliography please visit our website.

3-Methyl-5-AIQ . HCl
ALX-270-450-M001
1 mg
ALX-270-450-M005
5 mg
Water-soluble, potent inhibitor of poly(ADPribose) polymerase-1 (PARP-1) (IC50=0.23μM)
in vitro. Exhibits outstanding therapeutic benefits in models of myocardial infarction, ischaemia-reperfusion of the liver and kidney,
heart transplantation and acute lung inflammation.
LIT: Synthesis and PARP-1 inhibitory activity of 3-substituted analogues of the potent water-soluble PARP inihbitor 5-aminoisoquinolin-1-one (5-AIQ): E. C. Y. Woon, et al.; Bioorg. Med. Chem. (submitted), (2006)

3-Aminobenzamide
ALX-270-044-G001
1g
ALX-270-044-G005
5g
Inhibitor of poly(ADP-ribose) polymerase-1(PARP-1). Has minimal effect on bacterial
toxin-mediated ADP-ribosylation. Apoptosis
inhibitor.
LIT: Cell death protection by 3-aminobenzamide and other poly(ADPribose)polymerase inhibitors: different effects on human natural killer
and lymphokine activated killer cell activities: D. Monti, et al.; BBRC
199, 525 (1994)  For a comprehensive bibliography please visit
our website.

ABT-888

3-Methyl-5-AIQ . HCl

5-AIQ . HCl

6

4-Amino-1,8-naphthalimide

DR2313

ALX-270-250-M010
10 mg
Potent inhibitor of poly(ADP-ribose) polymerase-1 (PARP-1) (IC50=0.18μM). About 1000-foldmore potent than 3-aminobenzamide (Prod.
No. ALX-270-044).

ALX-270-452-M001
1 mg
ALX-270-452-M005
5 mg
ALX-270-452-M025
25 mg
Potent, water soluble competitive PARP inhibitor (IC50=0.20μM and 0.24μM for PARP-1 and
PARP-2 respectively).

LIT: Specific inhibitors of poly(ADP-ribose) synthetase and mono(ADPribosyl)transferase: M. Banasik, et al.; J. Biol. Chem. 267, 1569 (1992)
 4-Amino-1,8-naphthalimide: a novel inhibitor of poly(ADP-ribose)polymerase and radiation sensitizer: A. Schlicker, et al.; Int. J. Radiat. Biol. 75, 91 (1999)  For a comprehensive bibliography please
visit our website.

LIT: A newly synthesized poly(ADP-ribose) polymerase inhibitor,
DR2313 [2-methyl-3,5,7,8-tetrahydrothiopyrano[4,3-d]-pyrimidine4-one]: pharmacological profiles, neuroprotective effects, and therapeutic time window in cerebral ischemia in rats: H. Nakajima, et al.;Pharmacol. Exp. Ther. 312, 472 (2005)

Benzamide

EB-47 . 2HCl . 2H2O

ALX-270-174-G005
5g
Inhibitor of poly(ADP-ribose) polymerase-1(PARP-1). Neuroprotectant.
LIT: Cytotoxicity of a new IMP dehydrogenase inhibitor, benzamide riboside, to human myelogenous leukemia K562 cells: H.N.
Jayaram, et al.; BBRC 186, 1600 (1992)  Nitric oxide activationof poly(ADP-ribose) synthetase in neurotoxicity: J. Zhang, et al.;Science 263, 687 (1994)

DPQ[3,4-Dihydro-5-[4-(1-piperidinyl)butoxy]-1(2H)-isoquinolinone]

ALX-270-221-M001
1 mg
ALX-270-221-M005
5 mg
Very potent poly(ADP-ribose) polymerase-1(PARP-1) inhibitor.
LIT: Dihydroisoquinolines: the design and synthesis of a new seriesof potent inhibitors of poly(ADP-ribose) polymerase: M.J. Suto, etal.; Anticancer Drug Des. 6, 107 (1991)  Comet assay as a novel approach for studying DNA damage in focal cerebral ischemia: differential effects of NMDA receptor antagonists and poly(ADP-ribose)polymerase inhibitors: L. Giovannelli, et al.; J. Cereb. Blood Flow Metab. 22, 697 (2002)  For a comprehensive bibliography please
visit our website.

3-(4-Chlorophenyl)quinoxaline-5-carboxamide
ALX-270-486-M005
5 mg
Potent quinoxaline-based PARP inhibitorwith a 5–fold selectivity towards PARP-2(IC50=7nm) over PARP-1 (IC50=33nM). Brainpermeant. Exhibits good pharmacokinetics.
LIT: Discovery of quinazolinone and quinoxaline derivatives aspotent and selective poly(ADP-ribose) polymerase-1/2 inhibitors: A. Iwashita, et al.; FEBS Lett. 579, 1389 (2005)  Discovery ofpotent and selective PARP-1 and PARP-2 inhibitors: SBDD analysis via a combination of X-ray structural study and homology
modeling: J. Ishida, et al.; Bioorg. Med. Chem. 14, 1378 (2006)

ALX-270-383-M001
1 mg
ALX-270-383-M005
5 mg
Very potent and water soluble PARP-1 inhibitor(IC50=45nM, 100% inhibition at 200nM). Shows
cytoprotective effects against oxidative damage in cells and in vivo models of reperfusion
injury and inflammation.
LIT: The discovery and synthesis of novel adenosine substituted
2,3-dihydro-1H-isoindol-1-ones: potent inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1): P.G. Jagtap, et al.; Bioorg. Med. Chem.
Lett. 14, 81 (2004)

Latest Insight
PARP-2 Specific Inhibitor
PARP-1 and PARP-2 are poly(ADP-ribose)polymerases, which are involved in themaintenance of genomic integrity underconditions of genotoxic stimuli. The presence of two PARP enzymes that are bothactivated by DNA breaks, raises questions
about their individual roles under pathological conditions. R. Pellicciari, et al. recently identified a new potent and selective PARP-2 inhibitor 5-benzoyloxyisoquinolin-1(2H)-one, with 60-fold selectivity
for PARP-2 over PARP-1. This new inhibitor
can be used for further characterization of
PARP-2 in pathophysiological conditions.
LIT: On the Way to Selective PARP-2 Inhibitors. Design, Synthesis, and Preliminary Evaluation of a Series of Isoquinolinone Derivatives: R. Pellicciari, et al.;ChemMedChem, Epub ahead of print,(2008)

3-(4-Chlorophenyl)
quinoxaline-5-carboxamide

DR23134-Amino-1,8naphthalimide

3-Aminobenzamide

Benzamide

DPQ

EB-47 . 2HCl . 2H2O

For updated prices and additional information visit www.alexis-biochemicals.com, contact your local distributor, or call +41 61 926 89 89.

4-Hydroxyquinazoline

NU1025

ALX-270-279-G001
1g
Inhibitor of poly(ADP-ribose) polymerase-1(PARP-1).

[8-Hydroxy-2-methylquinazoline-4-one]

LIT: Regulation of kinase cascades and transcription factors by apoly(ADP-ribose) polymerase-1 inhibitor, 4-hydroxyquinazoline, in
lipopolysaccharide-induced inflammation in mice: B. Veres, et al.;J. Pharmacol. Exp. Ther. 310, 247 (2004)  Critical role of PI3-kinase/
Akt activation in the PARP inhibitor induced heart function recovery during ischemia-reperfusion: K. Kovacs, et al.; Biochem. Pharmacol. 71, 441 (2006)

5-Iodo-6-amino-1,2-benzopyrone
ALX-270-278-M001
1 mg
ALX-270-278-M005
5 mg
Inhibitor of poly(ADP-ribose) polymerase-1(PARP-1).
LIT: Reversion of malignant phenotype by 5-iodo-6-amino-1,2benzopyrone a non-covalently binding ligand of poly(ADP-ribose)polymerase: P.I. Bauer, et al.; Biochimie 77, 374 (1995)  Cancer cellselectivity of 5-iodo-6-aminobenzopyrone (INH2BP) and methyl-3,5diiodo-4(4’-methoxyphenoxy) benzoate (DIME): E. Kirsten & E. Kun;
Int. J. Mol. Med. 5, 279 (2000)  Role of poly(ADP-ribose) synthetaseactivation in the development of experimental allergic encephalomyelitis: G.S. Scott, et al.; J. Neuroimmunol. 117, 78 (2001)  Inhibition of poly (ADP-ribose) synthetase by gene disruption or inhibition
with 5-iodo-6-amino-1,2-benzopyrone protects mice from multiplelow-dose-streptozotocin-induced diabetes: J.G. Mabley, et al.; Br. J.
Pharmacol. 133, 909 (2001)  For a comprehensive bibliography
please visit our website.

1,5-Isoquinolinediol
ALX-480-039-M005
5 mg
ALX-480-039-M025
25 mg
Potent inhibitor of inducible nitric oxide synthase (iNOS; NOS II) in mouse macropaghes.
Potently blocks poly(ADP-ribose) polymerase-1 (PARP-1). Neuroprotectant.
LIT: Specific inhibitors of poly(ADP-ribose) synthetase and mono(ADPribosyl)transferase: M. Banasik, et al.; J. Biol. Chem. 267, 1569 (1992) 
Nitric oxide activation of poly(ADP-ribose) synthetase in neurotoxicity: J. Zhang, et al.; Science 263, 687 (1994)  All trans retinoic acidinduces apoptosis in acute promyelocytic NB4 cells when combinedwith isoquinolinediol, a poly(ADP-ribose) polymerase inhibitor: D.M.
Berry, et al.; Leuk. Res. 24, 307 (2000)  For a comprehensive bibliography please visit our website.

Latest Insight

ALX-270-370-M001
1 mg
ALX-270-370-M005
5 mg
ALX-270-370-M025
25 mg
A potent poly(ADP-ribose) polymerase 1(PARP-1) inhibitor (IC50=400nM) that potentiates the cytotoxicity of various DNA-active
agents, including the DNA-methylating compound MTIC, the DNA strand break-inducing
drug temozolomide (Prod. No. ALX-420-044),
topotecan (Prod. No. ALX-350-133), bleomycin(Prod. No. ALX-630-107), and ionizing radiation.

New Target for PARP Inhibition

LIT: Potentiation of anti-cancer agent cytotoxicity by the potentpoly(ADP-ribose) polymerase inhibitors NU1025 and NU1064: K.J.
Bowman, et al.; Br. J. Cancer 78, 1269 (1998)  Potentiation of temozolomide and topotecan growth inhibition and cytotoxicity by
novel poly(adenosine diphosphoribose) polymerase inhibitors in apanel of human tumor cell lines: C.A. Delaney, et al.; Clin. Cancer
Res. 6, 2860 (2000)  For a comprehensive bibliography please
visit our website.

Pigment epithelium-derived factor (PEDF)
acts as a strong endogenous inhibitor of angiogenesis and reactive oxygen species generation in cell culture, and plays a protectiverole in the development and progression ofangiogenic diseases. Recently, H. Chen, et al.
showed that PARP inhibition with the specific inhibitor PJ-34 upregulates hyperglycemia-induced PEDF expression in HUVECs
in a dose-dependent manner. This resulted
in delayed activation of p38 MAP kinase anda concomitant decrease in apoptosis. Theirresults demonstrated that PEDF might represent a target for PARP inhibition.

6(5H)-Phenanthridinone

LIT: Upregulation of PEDF expression by PARP inhibition contributes to the decrease in hyperglycemia-induced apoptosis
in HUVECs: H. Chen, et al.; BBRC 369, 718 (2008)

ALX-270-251-M010
10 mg
Poly(ADP-ribose)polymerase (PARP) inhibitor.

PJ-34

LIT: Specific inhibitors of poly(ADP-ribose) synthetase and mono(ADPribosyl)transferase: M. Banasik, et al.; J. Biol. Chem. 267, 1569 (1992) 
Effect of 6(5H)-phenanthridinone, a poly (ADP-ribose)polymerase inhibitor, and ionizing radiation on the growth of cultured lymphoma
cells: D. Weltin, et al.; Int. J. Radiat. Biol. 72, 685 (1997)  For a comprehensive bibliography please visit our website.

ALX-270-289-M001
1 mg
ALX-270-289-M005
5 mg
ALX-270-289-M025
25 mg
Potent, water-soluble poly(ADP-ribose)polymerase (PARP) inhibitor (EC50=20nM).
Inhibits peroxynitrite (Prod. No. ALX-400036)-induced cell necrosis (EC50=20nM).
Has significant, dose-dependent, anti-inflammatory effects in a variety of local inflammation models and provides cardioprotection by decreasing myocardial infarct size.

TIQ-A[Thieno[2,3-c]isoquinolin-5-one]

ALX-270-365-M001
1 mg
ALX-270-365-M005
5 mg
Potent poly(ADP-ribose) polymerase-1 (PARP-1)
inhibitor (IC50=450nM). Neuroprotectant.
LIT: Novel isoquinolinone-derived inhibitors of poly(ADP-ribose)polymerase-1: pharmacological characterization and neuroprotective effects in an in vitro model of cerebral ischemia: A. Chiarugi, etal.; J. Pharmacol. Exp. Ther. 305, 943 (2003)  Towards new neuroprotective agents: design and synthesis of 4H-thieno[2,3-c] isoquinolin-5-one derivatives as potent PARP-1 inhibitors: R. Pellicciari, etal.; Farmaco 58, 851 (2003)

LIT: Protective effects of PJ34, a novel, potent inhibitor ofpoly(ADP-ribose) polymerase (PARP) in in vitro and in vivo models of stroke: G.E. Abdelkarim, et al.; Int.
J. Mol. Med. 7, 255 (2001)  Activationof poly(ADP-ribose) polymerase contributes to the endothelial dysfunction
associated with hypertension and aging: P. Pacher, et al.; Int. J. Mol. Med. 9,659 (2002)  For a comprehensive bibliography please visit our website.

Minocycline . HCl
ALX-380-109-M050
50 mg
Semisynthetic. Tetracycline derivative with
antimicrobial activity. Inhibitor of angiogenesis, apoptosis and poly(ADP-ribose)polymerase-1 (PARP-1). Anti-inflammatory
and neuroprotective.
LIT: Minocycline up-regulates Bcl-2 and protects against cell deathin mitochondria: J. Wang, et al.; J. Biol. Chem. 279, 19948 (2004) 
Minocycline inhibits poly(ADP-ribose) polymerase-1 at nanomolar
concentrations: C.C. Alano, et al.; PNAS 103, 9685 (2006)  Multiple
neuroprotective mechanisms of minocycline in autoimmune CNS
inflammation: K. Maier, et al.; Neurobiol. Dis. 25, 514 (2007)  For acomprehensive bibliography please visit our website.

Nicotinamide
ALX-460-008-G010

10 g

TH E PA RP FA MI LY

International Edition

PARG Inhibitor
ADP-HPD . ammonium salt . dihydrate
ALX-480-094-C060
60 μg
Potent, noncompetitive, and specific inhibitor of poly(ADP-ribose) glycohydrolase (PARG)(IC50=120nM) versus ADP-ribose (IC50=120μM).
Does not affect the activities of either PARP-1
or NAD:arginine mono(ADP-ribosyl)-transferase A even at 1mM concentration.

PARP Activator

LIT: Specific inhibition of poly(ADP-ribose) glycohydrolase by adenosine diphosphate (hydroxymethyl)pyrrolidinediol: J.T. Slama, et al.; J.
Med. Chem. 38, 389 (1995)  Mechanism of inhibition of poly(ADPribose) glycohydrolase by adenosine diphosphate (hydroxymethyl)pyrrolidinediol: J.T. Slama, et al.; J. Med. Chem. 38, 4332 (1995)  A
cellular defense pathway regulating transcription through poly(ADPribosyl)ation in response to DNA damage: S. Vispe, et al.; PNAS 97,
9886 (2000)

LIT: DNA damage induced by peroxynitrite: subsequent biologicaleffects: C. Szabo & H. Ohshima; Nitric Oxide 1, 373 (1997)  Peroxynitrite: a biologically significant oxidant: M.P. Murphy, et al.; Gen.
Pharmacol. 31, 179 (1998)

Peroxynitrite . tetramethylammonium
ALX-400-036-L001
1 ml
ALX-400-036-5001
5 x 1 ml
This formulation of peroxynitrite has a low
nitrite content (~1%), no hydrogen peroxide.

Peroxynitrite . tetramethylammonium

4-Hydroxyquinazoline

Nicotinamide
6(5H)-Phenanthridinone

1,5-Isoquinolinediol

5-Iodo-6-amino-1,2-benzopyrone. 2H2O

Minocycline . HCl

NU1025

Purified (PF) = Purified (Preservative free); FC = Flow Cytometry; ICC = Immunocytochemistry; IP = Immunoprecipitation;
IHC = Immunohistochemistry (FS = Frozen Sections, PS = Paraffin Sections); WB = Western blot; BP = Blocking Peptide

TIQ-A

ADP-HPD . ammonium salt

7

TH E PA RP FA MI LY

International Edition

Sirtuins
Sirtuins (SIRTs 1-7), or class III histone deacetylases (HDACs), are NAD+-dependent enzymes
that target a wide range of cellular proteins in
the nucleus, cytoplasm, and mitochondrium forpost-translational modification by deacetylation (SIRT1, -2, -3 and -5) and/or ADP ribosylation (SIRT2, -3, -4 and -6). Sirtuins are involved
in important biological processes ranging from
apoptosis, cancer prevention, DNA damage repair, and regulation of energy expenditure to
stress resistance.
SIRT1 has been shown to deacetylate severaltranscription factors, including the tumor suppressor protein p53, members of the FOXO family, HES-1 and HEY-2, PPAR-γ, MyoD, CTIP2, p300,
PGC-1α, and NF-κB and has been linked to theregulation of aging. The functional interplay of
SIRT1 and PARP-1 in response to DNA damage
results in AIF (apoptosis inducing factor)-mediated cell death. These findings establish a functional link between the two NAD+-dependent
enzyme systems and provide a physiologicalinterpretation for the mechanism of death incells lacking SIRT1.
SIRT2 was shown to deacetylate α-tubulin andco-localizing with the cytoplasmic tubulin network, being involved in development. It also
showed neuroprotective functions, controls insulin/IGF-1 levels in the cytoskeleton of Alzheimer disease and deacetylates p53 in the cytoplasm. The role of sirtuins in controlling basic
cellular functions generated efforts in the development of small-molecule regulators thatmodulate their cellular function. Compounds
that target sirtuins may be useful in the treatment of many diseases.

Standard Inhibitor
Sirtinol[2-[(2-Hydroxynaphthalen-1-yl-methylene)amino]-N-(1phenethyl)benzamide]

ALX-270-308-M001
1 mg
ALX-270-308-M005
5 mg
Specific cell permeable inhibitor of the sirtuin family of NAD-dependent deacetylases(ySir2: IC50=48μM; hSIRT1: IC50=131μM;
hSIRT2: IC50=58μM) with no effect on human HDAC1. Reported to inhibit Sir2ptranscriptional silencing activity in vivo
(IC50=25μM) and NAD-dependent histone
deacetylase activity of purified recombinant yeast Sir2p (IC50=70μM) and hSIRT2(IC50=40μM) in vitro.
LIT: Identification of a class of small molecule inhibitors of thesirtuin family of NAD-dependent deacetylases by phenotypic
screening: C.M. Grozinger, et al.; J. Biol. Chem. 276, 38837 (2001)
 Human telomeric position effect is determined by chromosomal context and telomeric chromatin integrity: C.E. Koering,
et al.; EMBO Rep. 3, 1055 (2002)  Design, synthesis, and biological evaluation of sirtinol analogues as class III histone/protein
deacetylase (Sirtuin) inhibitors: A. Mai, et al.; J. Med. Chem. 48,
7789 (2005)  Sirt1 inhibitor, Sirtinol, induces senescence-likegrowth arrest with attenuated Ras-MAPK signaling in humancancer cells: H. Ota, et al.; Oncogene 25, 176 (2006)

Antibodies
PAb to SIRT1 (25-75) (human)

PAb to SIRT2 (1-50) (human)

BET-A300-687A
0.02 mg
From rabbit. IMMUNOGEN: Synthetic peptide corresponding to aa 25-75 of human SIRT1 (NADdependent deacetylase sirtuin-1). SPECIFICITY:
Recognizes human SIRT1. APPLICATION: IP, WB.
BP: BET-BP300-687.

BET-A300-702A
0.1 mgFrom rabbit. IMMUNOGEN: Synthetic peptide corresponding to aa 1-50 of human SIRT2 (NADdependent deacetylase sirtuin-2). SPECIFICITY:
Recognizes human SIRT2. APPLICATION: IP, WB.
BP: BET-BP300-702.

PAb to SIRT1 (700-747) (human)

PAb to SIRT2 (350-389) (human)

BET-A300-688A
0.02 mg
From rabbit. IMMUNOGEN: Synthetic peptide corresponding to aa 700-747 of C-terminal human
SIRT1 (NAD-dependent deacetylase sirtuin-1).
SPECIFICITY: Recognizes human SIRT1. APPLICA
TION: IP, WB. BP: BET-BP300-688.

BET-A300-703A
0.1 mgFrom rabbit. IMMUNOGEN: Synthetic peptide corresponding to aa 350-389 of C-terminal human
SIRT2 (NAD-dependent deacetylase sirtuin-2).
SPECIFICITY: Recognizes human SIRT2. APPLICA
TION: IP. BP: BET-BP300-703.

Inhibitors
AGK2

B2

ALX-270-484-M001
1 mg
ALX-270-484-M005
5 mg
Potent, selective and cell permeable inhibitor of sirtuin 2 (SIRT2) (IC50=3.5μM). Rescues
α-synuclein-mediated toxicity. Modifies inclusion morphology in a cellular model of Parkinson’s disease. Protects against dopaminergic
cell death. Leads to an increase in acetylated
tubulin.
LIT: Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity inmodels of Parkinson’s disease: T.F. Outeiro, et al.; Science 317, 516(2007)

Aristoforin
ALX-350-129-M001
1 mg
Stable and water-soluble derivative of hyperforin (Prod. No. ALX-350-097) inducing apoptosis. Antitumor agent. Inhibits sirtuins.
LIT: Aristoforin, a novel stable derivative of hyperforin, is a potent
anticancer agent: M. Gartner, et al.; Chembiochem. 6, 171 (2005) 
Phloroglucinol Derivatives Guttiferone G, Aristoforin, and Hyperforin:
Inhibitors of Human Sirtuins SIRT1 and SIRT2: C. Gey, et al.; Angew.
Chem. Int. Ed. Engl. 46, 5219 (2007)

ALX-270-485-MC05
0.5 mgCell permeable inhibitor of sirtuin 2 (SIRT2)(IC50=35μM). Promotes inclusion formation incellular models of both Huntington’s disease
and Parkinson’s disease. Prevents huntingtinmediated proteasome dysfunction and reduces α-synuclein-mediated toxicity.
LIT: Pharmacological promotion of inclusion formation: a therapeutic approach for Huntington’s and Parkinson’s diseases: R.A. Bodner,
et al.; PNAS 103, 4246 (2006)

6-Chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide
ALX-270-437-M001
1 mg
Potent cell permeable and metabolically stable specific inhibitor of hSIRT1 (IC50=98nM invivo / IC50=38nM in vitro; compared to hSIRT2:
IC50=19μM and hSIRT3: IC50=48μM) with no effect on human histone deacetylases (HDACs)
class I and class II, nor NAD glycohydrolase(IC50>100μg). Inhibits the deacetylation of
p53 (IC50=1μM).
LIT: Discovery of indoles as potent and selective inhibitors of thedeacetylase SIRT1: A.D. Napper, et al.; J. Med. Chem. 48, 8045
(2005)

6-Chloro-2,3,4,9-tetrahydro1H-carbazole-1-carboxamide

AGK2
B2

Aristoforin

Selected Latest Review Articles
The Sir 2 family of protein deacetylases: J.M. Denu; Curr. Opin.
Chem. Biol. 9, 431 (2005)  Sirtuins (histone deacetylases III) in
the cellular response to DNA damage – facts and hypotheses:
M. Kruszewski & I. Szumiel; DNA Repair (Amst) 4, 1306 (2005) 
Neuronal protection by sirtuins in Alzheimer‘s disease: T.S. Anekonda & P.H. Reddy; J. Neurochem. 96, 305 (2006)  Sirt1: a metabolic master switch that modulates lifespan: I.B. Leibiger & P.O.
Berggren; Nat. Med. 12, 34 (2006)  The molecular biology of

8[CPNQ; 5-[4-(4-Chlorobenzoyl)-1-piperazinyl]-8-nitroquinoline]

mammalian SIRT proteins: SIRT2 in cell cycle regulation: T. Inoue,
et al.; Cell Cycle 6, 1011 (2007)  Sirtuin functions in health anddisease: H. Yamamoto, et al.; Mol. Endocrinol. 21, 1745 (2007)  Sirtuins, nuclear hormone receptor acetylation and transcriptional
regulation: J.R. Whittle, et al.; Trends Endocrinol. Metab. 18, 356(2007)  Conserved metabolic regulatory functions of sirtuins: B.
Schwer & E. Verdin; Cell Metab. 7, 104 (2008)

For updated prices and additional information visit www.alexis-biochemicals.com, contact your local distributor, or call +41 61 926 89 89.

TH E PA RP FA MI LY

International Edition

NAD+ Metabolism
ADP-Ribosylation
Nuclear ADP-ribosylation reactions are criticalfor many physiological and pathophysiologicaloutcomes, such as cellular differentiation andproliferation, genome integrity, carcinogenesis,
cell survival and cell death, inflammation, andneuronal functions.
An interesting feature is the potential cross talkof mono- and poly-ADP-ribosylation reactions
and other NAD+-dependent reactions, either
directly through trans-ADP-ribosylation or indirectly through modulation of the NAD+ levels.
Cross talk of SIRT1 and poly-ADP-ribosylation reactions may provide balance between
cell survival and cell death, longevity, andsenescence. Moreover, SIRTs and mono- or
poly-ADP-ribosylation pathways may provide
a unified network for multicellular eukaryotes
to deal with nutritional supply and environmental stress.
Various studies suggested different molecularmechanisms for how mono- and poly-ADP-ribosylation reactions are integrated in diverse
physiological processes. Mono- and poly-ADPribosylation reactions may act on the level ofsignalling, modulation of chromatin structure,and epigenetic histone code.

Selected Review Article
Nuclear ADP-ribosylation reactions in mammalian cells: where are
we today and where are we going?: P.O. Hassa, et al.; Microbiol. Mol.
Biol. Rev. 70, 789 (2006)

NAD: New Insights on a Key
Signalling Player!
The pyridine nucleotides NAD and phosphorylated NAD (NADP) are major redox carriers inall organisms. Recent years have shown an increase of signalling and gene regulatory processes where NAD+ or NADP are metabolised.
NAD+ serves as substrate for protein modification including protein deacetylation, andmono- and poly-ADP-ribosylation, while both
NAD+ and NADP represent precursors of intracellular calcium-mobilizing molecules. It is beyond doubt that NADP-mediated signal transduction does not only regulate metabolic pathways, but holds a key position in the control offundamental cellular processes. NAD+ kinases
phosphorylate NAD+ to NADP and have potential roles in stress signalling and ROS generation. Components such as nicotinamide mononucleotide adenylyltransferase-1 (NMNAT1),
which is involved in the NAD+-salvage pathway,
and PARG might also contribute locally to thefine-tuning and the persistence, respectively,of PAR signalling at DNA-damage sites

FIGURE: Adapted from Poly(ADP-ribose): novel functions for an old molecule: V. Schreiber, et al.; Nat. Rev. Mol. Cell Biol. 7, 517 (2006)

Highly Pure & Fully Active NAD Kinases
NAD Kinase (full length) (active)(human) (rec.) (His)NAD Kinase (NT truncated) (active)(human) (rec.) (His)

ALX-201-235-C050
50 μg
Produced in E. coli. Human NADK is fused at
the N-terminus to a His-tag. QUANTITY: Sufficient for the preparation of >10μmol of NADP
from NAD and ATP in 1ml of a 10mM solution. Free of any nucleotide converting sideactivities.

ALX-201-236-C050
50 μg
Produced in E. coli. Human NADK (aa 64-446)
is fused at the N-terminus to a His-tag. QUAN
TITY: Sufficient for the preparation of >10μmolof NADP from NAD and ATP in 1ml of a 10mM
solution. Free of any nucleotide converting
side-activities.

LIT: Structural and functional characterization of human NAD kinase: F. Lerner, et al.; BBRC 288, 69 (2001)

LIT: Structural and functional characterization of human NAD kinase: F. Lerner, et al.; BBRC 288, 69 (2001)

NMNAT1 (human) (rec.) (His)

NMNAT3 (human) (rec.) (His)
ALX-201-238-C100
100 μgProduced in E. coli. Full length human NMNAT3
is fused at the N-terminus to a His-tag. APPLICA
TION: Well suited for the synthesis of NAD analogs due to lower substrate selectivity compared to NMNAT1 (human) (recombinant)(Prod. No. ALX-201-237).

Selected Review Articles

ALX-201-237-C100
100 μgProduced in E. coli. Full length human NMNAT1
is fused at the N-terminus to a His-tag. APPLICATION: Well suited for the synthesis of NAD
due to high specific activity (10-20U/mg)
and high substrate selectivity compared to
NMNAT3 (human) (recombinant) (Prod. No.
ALX-201-238).

The new life of a centenarian: signalling functions of NAD(P): F.
Berger, et al.; TIBS 29, 111 (2004)  A vital link between energy andsignal transduction: M. Ziegler; FEBS J. 272, 4561 (2005)  NAD+and NADH in cellular functions and cell death: W. Ying; Front. Biosci. 11, 3129 (2006)

LIT: Molecular cloning, chromosomal localization, tissue mRNAlevels, bacterial expression, and enzymatic properties of human
NMN adenylyltransferase: M. Emanuelli, et al.; J. Biol. Chem. 276,406 (2001)  For a comprehensive bibliography please visit our
website.

Purified (PF) = Purified (Preservative free); FC = Flow Cytometry; ICC = Immunocytochemistry; IP = Immunoprecipitation;
IHC = Immunohistochemistry (FS = Frozen Sections, PS = Paraffin Sections); WB = Western blot; BP = Blocking Peptide

LIT: Structural characterization of a human cytosolic NMN/NaMN
adenylyltransferase and implication in human NAD biosynthesis:
X. Zhang, et al.; J. Biol. Chem. 278, 13503 (2003)  Subcellular compartmentation and differential catalytic properties of the three human nicotinamide mononucleotide adenylyltransferase isoforms:
F. Berger, et al.; J. Biol. Chem. 280, 36334 (2005)

9

TH E PA RP FA MI LY

International Edition

NAD+ Metabolism

continued
ART ProteinsART2.1 (rat) (rec.) (His)[ecto-ADP-ribosyltransferase 1 (rat) (rec.) (His); ART2a(rat) (rec.) (His); RT6.1 (rat) (rec.) (His)]

ALX-201-287-C010
Produced in E. coli.

10 μg

LIT: Structure of the ecto-ADP-ribosyl transferase ART2.2 fromrat: C. Mueller-Dieckmann, et al.; J. Mol. Biol. 322, 687 (2002) 
Substrate binding and catalysis of ecto-ADP-ribosyltransferase
2.2 from rat: H. Ritter, et al.; Biochemistry 42, 10155 (2003)

ART2.2 (rat) (rec.) (His)[ecto-ADP-ribosyltransferase 2 (rat) (rec.) (His); ART2b(rat) (rec.) (His); RT6.2 (rat) (rec.) (His)]

ALX-201-288-C010
Produced in E. coli.

10 μg

LIT: Expression, purification, crystallization and preliminary X-ray
analysis of rat ecto-ADP-ribosyltransferase 2 (ART2.2): C. MuellerDieckmann, et al.; Acta Crystallogr. D. Biol. Crystallogr. 58, 1211
(2002)  Structure of the ecto-ADP-ribosyl transferase ART2.2
from rat: C. Mueller-Dieckmann, et al.; J. Mol. Biol. 322, 687 (2002)
 Substrate binding and catalysis of ecto-ADP-ribosyltransferase
2.2 from rat: H. Ritter, et al.; Biochemistry 42, 10155 (2003)

FIGURE: Posttranslational modification of proteins by reversible ADP-ribosylation. Adapted from: The structure of human ADP-ribosylhydrolase 3 (ARH3) provides insights into the reversibility of protein ADP-ribosylation: C. Mueller-Dieckmann, et al.; PNAS 103, 15026 (2006)

NAD-dependent ADP-ribosylation
NAD-dependent ADP-ribosylation is a reversible posttranslational modification involved inmany cellular processes including DNA-repair,transcription, telomere function and apoptosis. Mono- and poly-ADP-ribosyltransferases(mARTs and pARTs/PARPs) catalyze the transfer of the ADP-ribose moiety from NAD+ onto
specific amino acid side chains in target proteins under the release of nicotinamide. This
modification may lead to either activation or inactivation of the target protein. In contrast, protein-ADP-ribosylhydrolases (ARHs and PARGs)
hydrolyze the α-glycosidic bond between ADPribose and the side chain, thereby restoring
normal protein function (Figure) [1, 2].

Mono-ADP-ribosyltransferases(ARTs; mARTs)
Enzyme-modulated mono(ADP-ribosyl)ation
was originally identified as the mechanism ofaction of several bacterial toxins [1]. The cholera,
diphteria and pertussis toxins are mono-ADPribosyltransferases (ARTs; mARTs; EC 2.4.2.31),
known to cause various pathologies after theirtranslocation into mammalian host cells. These
toxins interfere with protein synthesis, signaltransduction, or cytoskeletal functions by ADPribosylating key target proteins such as elongation factor 2, G proteins, or actin.
Mammalian ARTs constitute a family of structurally related proteins expressed on the cell surface or secreted in the extracellular compartment. Five paralogs (ART1-5) have been cloned.
Only four of them are expressed in human due
to a defective ART2 gene, and six in the mouseas the result of ART2 gene duplication (ART2.1,
ART2.2) [3]. ARTs are expressed in different tissues and are involved in many physiologicalprocesses, such as myogenesis and innate aswell as adaptive immunity [4].

10ART2.2 (mouse) (rec.) (His)[ecto-ADP-ribosyltransferase 2.2 (mouse) (rec.) (His);
ART2b (mouse) (rec.) (His)]

The ART substrate NAD gets released from damaged cells during inflammation. Upon exposureof T cells to NAD, ART2 catalyzes ADP-ribosylation of the purinergic receptor P2X7 and other functionally important cell surface proteins.
ADP-ribosylation activates P2X7, triggering calcium flux, exposure of phosphatidylserine, andformation of large membrane pores, ultimately
resulting in apoptosis [5-7]. In the extracellularenvironment, the signalling function of NAD
is controlled by NAD-degrading ectoenzymes
such as CD38 [8].

ADP-ribosylhydrolases (ARHs)
Three different ADP-ribosylhydrolases (ARH1-3)
have been identified in human so far. ARH1 specifically hydrolyzes ADP-ribosylarginine, whereas ARH3 degrades poly-ADP-ribose but does
not cleave ADP-ribosyl-asparagine, -diphthamide, or –cysteine bonds. In addition, ARH3 catalyzes the production of ADP-ribose from Oacetyl-ADP-ribose. The exact function of ARH2
has not been determined so far [9, 10].
LIT: [1] ADP-ribosylation: K. Ueda & O. Hayaishi; Annu. Rev. Biochem.
54, 73 (1985)  [2] The structure of human ADP-ribosylhydrolase 3(ARH3) provides insights into the reversibility of protein ADP-ribosylation: C. Mueller-Dieckmann, et al.; PNAS 103, 15026 (2006)  [3]The family of toxin-related ecto-ADP-ribosyltransferases in humans
and the mouse: G. Glowacki, et al.; Protein Sci. 11, 1657 (2002)  [4]Use of genetic immunization to raise antibodies recognizing toxinrelated cell surface ADP-ribosyltransferases in native conformation:
F. Koch-Nolte, et al.; Cell Immunol. 236, 66 (2005)  [5] NAD-induced
T cell death: ADP-ribosylation of cell surface proteins by ART2 activates the cytolytic P2X7 purinoceptor: M. Seman, et al.; Immunity 19,
571 (2003)  [6] Triggering of T-cell apoptosis by toxin-related ectoADP-ribosyltransferase ART2: F. Scheuplein, et al.; Ann. N. Y. Acad. Sci.
1010, 296 (2003)  [7] P2X7 receptor-dependent and -independent
T cell death is induced by nicotinamide adenine dinucleotide: H.
Kawamura, et al.; J. Immunol. 174, 1971 (2005)  [8] CD38 controls
ADP-ribosyltransferase-2-catalyzed ADP-ribosylation of T cell surface
proteins: C. Krebs, et al.; J. Immunol. 174, 3298 (2005)  [9] Identification and characterization of a mammalian 39-kDa poly(ADP-ribose)
glycohydrolase: S. Oka, et al.; J. Biol. Chem. 281, 705 (2006)  [10] The
39-kDa poly(ADP-ribose) glycohydrolase ARH3 hydrolyzes O-acetylADP-ribose, a product of the Sir2 family of acetyl-histone deacetylases: T. Ono, et al.; PNAS 103, 16687 (2006)

ALX-201-289-C010
Produced in E. coli.

10 μg

LIT: Regulation of glutamate dehydrogenase by reversible ADPribosylation in mitochondria: A. Herrero-Yraola, et al.; EMBO J. 20,2404 (2001)  Single domain antibodies from llama effectively
and specifically block T cell ecto-ADP-ribosyltransferase ART2.2
in vivo: F. Koch-Nolte, et al.; FASEB J. 21, 3490 (2007)

Related Products
Pertussis Toxin[Islet-Activating Protein; PTX; Holotoxin]

ALX-630-003-C050
50 μg
Isolated from Bordetella pertussis. Major
protein toxin produced by virulent strainsof Bordetella pertussis. The purified protein
consists of five dissimilar subunits: S-1 (MW28kDa), S-2 (MW 23kDa), S-3 (MW 22kDa),
S-4 (MW 11.7kDa) and S-5 (MW 9.3kDa), ina molar ratio of 1:1:1:2:1. S-1 (A protomer)
is responsible for the enzymatic activity ofthe toxin. Together, S-2, S-3, S-4 and S-5
comprise the B oligomer, responsible forbinding the toxin to the cell surface.
LIT: Subunit structure of islet-activating protein, pertussis toxin,
in conformity with the A-B model: M. Tamura, et al.; Biochemistry21, 5516 (1982)  Induction of a novel morphological response
in Chinese hamster ovary cells by pertussis toxin: E.L. Hewlett, etal.; Infect. Immun. 40, 1198 (1983)  Structure-activity analysisof the activation of pertussis toxin: H.R. Kaslow, et al.; Biochemistry 26, 123 (1987)  Pertussis toxin and target eukaryotic cells:binding, entry, and activation: H. R. Kaslow & D. L. Burns; FASEB
J. 6, 2684 (1992)  A proposed mechanism of ADP-ribosylation
catalyzed by the pertussis toxin S1 subunit: C. Locht & R. Antoine; Biochimie 77, 333 (1995)

SpvB (salmonella enterica)(rec.) (His)
ALX-201-294-C010
Produced in E. coli.

10 μg

LIT: The spvB gene-product of the Salmonella enterica virulence
plasmid is a mono(ADP-ribosyl)transferase: H. Otto, et al.; Mol.
Microbiol. 37, 1106 (2000)  A steric antagonism of actin polymerization by a salmonella virulence protein: S.M. Margarit, etal.; Structure 14, 1219 (2006)

For updated prices and additional information visit www.alexis-biochemicals.com, contact your local distributor, or call +41 61 926 89 89.

ART Antibodies

ARH Proteins

MAb to ART1 (human) (GUGU1-A3)

PAb to ART2.2 (mouse)

ALX-802-020-L001
1 ml
CLONE: GUGU1-A3. ISOTYPE: Rat IgG2b. IMMUNOGEN:
Vector containing the cDNA of human ART1
(ecto-ADP-ribosyltransferase 1; CD296). SPECIFICITY: Recognizes human ART1. APPLICATION: FC, ICC.

ALX-215-039-R100
100 μlFrom rabbit. IMMUNOGEN: Vector containing
the cDNA of mouse ART2.2 (ecto-ADP-ribosyltransferase 2.2; ART2b). SPECIFICITY: Recognizes mouse ART2.2. APPLICATION: FC, ICC. FUNC
(blocking).

LIT: Use of genetic immunization to raise antibodies recognizing
toxin-related cell surface ADP-ribosyltransferases in native conformation: F. Koch-Nolte, et al.; Cell. Immunol. 236, 66 (2005)

PAb to ART1 (human)
ALX-215-037-R100
100 μlFrom rabbit. IMMUNOGEN: Vector containing
the cDNA of human ART1 (ecto-ADP-ribosyltransferase 1; CD296). SPECIFICITY: Recognizes
human ART1. APPLICATION: FC, ICC.
LIT: See ALX-802-020

MAb to ART1 (mouse) (NOGU1-A111)
ALX-802-028-L001
1 ml
CLONE: NOGU1-A111. ISOTYPE: Rat IgG2a. IMMUNO
GEN: Vector containing the cDNA of mouse ART1
(ecto-ADP-ribosyltransferase 1; CD296). SPE
CIFICITY: Recognizes mouse ART1. APPLICATION:
FC, ICC.

PAb to ART1 (mouse)
ALX-215-038-R100
100 μlFrom rabbit. IMMUNOGEN: Vector containing thecDNA of mouse ART1 (ecto-ADP-ribosyltransferase 1; CD296). SPECIFICITY: Recognizes mouse
ART1. APPLICATION: FC, ICC.
LIT: See ALX-802-020

MAb to ART2.1 (mouse) (GUGU2-B54)
ALX-802-021-L001
1 ml
CLONE: GUGU2-B54. ISOTYPE: Rat IgG2a. IMMUNOGEN: Vector containing the cDNA of mouse
ART2.1 (ecto-ADP-ribosyltransferase 2.1;
ART2a). SPECIFICITY: Recognizes mouse ART2.1.
APPLICATION: FC, ICC.
LIT: See ALX-802-020

MAb to ART2.2 (mouse) (NIKA-102)
ALX-802-022-L001
1 ml
CLONE: NIKA-102. ISOTYPE: Rat IgG2a. IMMUNOGEN:
Vector containing the cDNA of mouse ART2.2(ecto-ADP-ribosyltransferase 2.2; ART2b). SPE
CIFICITY: Recognizes mouse ART2.2. APPLICATION:
FC, ICC.
LIT: A new monoclonal antibody detects a developmentally regulated mouse ecto-ADP-ribosyltransferase on T cells: subset distribution, inbred strain variation, and modulation upon T cell activation:
F. Koch-Nolte, et al.; J. Immunol. 163, 6014 (1999)

rAb (Single Domain, VHH) to
ART2.2 (mouse) (s+16a)
ALX-815-002-C050
50 μg
CLONE: s+16a. ISOTYPE: Llama IgG. IMMUNO
GEN: Recombinant mouse ART2.2 (ectoADP-ribosyltransferase 2.2; ART2b). SPECIFICITY: Recognizes mouse ART2.2. APPLICATION:
FUNC (blocking: effectively and specifically
blocks ART2.2 in vitro and in vivo).
LIT: Single domain antibodies from llama effectively and specifically block T cell ecto-ADP-ribosyltransferase ART2.2 in vivo:
F. Koch-Nolte, et al.; FASEB J. 21, 3490 (2007)

LIT: Rapid induction of naive T cell apoptosis by ecto-nicotinamide
adenine dinucleotide: requirement for mono(ADP-ribosyl)transferase
2 and a downstream effector: S. Adriouch, et al.; J. Immunol. 167,
196 (2001)  NAD-induced T cell death: ADP-ribosylation of cell surface proteins by ART2 activates the cytolytic P2X7 purinoceptor: M.
Seman, et al.; Immunity 19, 571 (2003)  Use of genetic immunization to raise antibodies recognizing toxin-related cell surface ADPribosyltransferases in native conformation: F. Koch-Nolte, et al.; Cell.
Immunol. 236, 66 (2005)

MAb to ART3 (human) (GUGU3-A51)
ALX-802-023-L001
1 ml
CLONE: GUGU3-A51. ISOTYPE: Rat IgG2a. IMMUNOGEN: Vector containing the cDNA of human
ART3 (ecto-ADP-ribosyltransferase 3). SPECIFICITY: Recognizes human ART3. APPLICATION: FC,
ICC.

ARH1 (human) (rec.) (His)[ADP-ribosylarginine Hydrolase (human) (rec.) (His); ADPRH(human) (rec.) (His)]

ALX-201-290-C010
Produced in E. coli.

10 μg

LIT: The structure of human ADP-ribosylhydrolase 3 (ARH3) provides
insights into the reversibility of protein ADP-ribosylation: C. MuellerDieckmann, et al.; PNAS 103, 15026 (2006)

TH E PA RP FA MI LY

International Edition

ARH1 (mouse) (rec.) (His)[ADP-ribosylarginine Hydrolase (mouse) (rec.) (His); Adprh(mouse) (rec.) (His)]

ALX-201-291-C010
Produced in E. coli.

10 μg

ARH3 (human) (rec.) (His)[ADP-ribosylhydrolase 3 (human) (rec.) (His); ADPRHL2(human) (rec.) (His)]

ALX-201-292-C010
Produced in E. coli.

10 μg

LIT: The structure of human ADP-ribosylhydrolase 3 (ARH3) provides
insights into the reversibility of protein ADP-ribosylation: C. MuellerDieckmann, et al.; PNAS 103, 15026 (2006)

LIT: Use of genetic immunization to raise antibodies recognizing
toxin-related cell surface ADP-ribosyltransferases in native conformation: F. Koch-Nolte, et al.; Cell. Immunol. 236, 66 (2005)  Expressionof toxin-related human mono-ADP-ribosyltransferase 3 in humantestes: M. Friedrich, et al.; Asian J. Androl. 8, 281 (2006)

MAb to ART3 (mouse) (GUGU3-A34)
ALX-802-024-L001
1 ml
CLONE: GUGU3-A34. ISOTYPE: Rat IgG2a. IMMUNOGEN: Vector containing the cDNA of mouse
ART3 (ecto-ADP-ribosyltransferase 3). SPECIFICITY: Recognizes mouse ART3. APPLICATION: FC,
ICC.
LIT: Use of genetic immunization to raise antibodies recognizing
toxin-related cell surface ADP-ribosyltransferases in native conformation: F. Koch-Nolte, et al.; Cell. Immunol. 236, 66 (2005)  Expressionof toxin-related human mono-ADP-ribosyltransferase 3 in humantestes: M. Friedrich, et al.; Asian J. Androl. 8, 281 (2006)

FIGURE: Crystal structure of human ARH3.

MAb to ART4 (human) (NONI-B4)
ALX-802-025-L001
1 ml
CLONE: NONI-B4. ISOTYPE: Rat IgG2a. IMMUNOGEN:
Vector containing the cDNA of human ART4
(ecto-ADP-ribosyltransferase 4; CD297). SPE
CIFICITY: Recognizes human ART4. APPLICATION:
FC, ICC.
LIT: A panel of monoclonal antibodies recognizing GPI-anchored
ADP-ribosyltransferase ART4, the carrier of the Dombrock bloodgroup antigens: I. Parusel, et al.; Cell Immunol. 236, 59 (2005)  Use
of genetic immunization to raise antibodies recognizing toxin-related cell surface ADP-ribosyltransferases in native conformation: F.
Koch-Nolte; Cell. Immunol. 236, 66 (2005)

PAb to ART4 (human)

ARH3 (mouse) (rec.) (His)[ADP-ribosylhydrolase 3 (mouse) (rec.) (His); Adprhl2 (mouse)(rec.) (His)]

ALX-201-293-C010
Produced in E. coli.

10 μg

LIT: Functional localization of two poly(ADP-ribose)-degrading enzymes to the mitochondrial matrix: M. Niere, et al.; Mol. Cell Biol. 28,
814 (2008)  Structure of mouse ADP-ribosylhydrolase 3 (mARH3): C.
Mueller-Dieckmann, et al.; Acta Crystallogr. Sect. F Struct. Biol. Cryst.
Commun. 64, 156 (2008)

Related Products

ALX-215-042-R100
100 μlFrom rabbit. IMMUNOGEN: Vector containing thecDNA of human ART4 (ecto-ADP-ribosyltransferase 4; CD297). SPECIFICITY: Recognizes humanART4. APPLICATION: FC, ICC.

β-Nicotinamide-1,N6-ethenoadenine
dinucleotide

LIT: See ALX-802-020

1,N6-Ethenoadenosine

MAb to ART4 (mouse) (GUGU4-A53)[ε-Ado]ALX-802-026-L001
1 ml
CLONE: GUGU4-A53. ISOTYPE: Rat IgG2a. IMMUNOGEN: Vector containing the cDNA of mouse
ART4 (ecto-ADP-ribosyltransferase 4; CD297).
SPECIFICITY: Recognizes mouse ART4. APPLICATION:
FC, ICC.

[ε-NAD +]BLG-N010-10

BLG-E011-10

10 μmol

10 μmolMore Information? Please visit

LIT: See ALX-802-020

Purified (PF) = Purified (Preservative free); FC = Flow Cytometry; ICC = Immunocytochemistry; IP = Immunoprecipitation;
IHC = Immunohistochemistry (FS = Frozen Sections, PS = Paraffin Sections); WB = Western blot; BP = Blocking Peptide

11

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Clone 10H– The Standard DNA Damage Detection Marker
MAb 10H

MAb to Poly(ADP-ribose) [PAR] (10H)
ALX-804-220-R100
100 μl
CLONE: 10H. ISOTYPE: Mouse IgG3. IMMUNOGEN: Purifiedpoly(ADP-ribose). SPECIFICITY: Recognizes poly(ADPribose) synthesized by a broad range of PARPs(poly(ADP-ribose) polymerases) like human, mouse,
rat or Drosophila PARP enzyme. APPLICATION: FC, ICC,
IHC (PS), WB.

DAPI Staining

H2O2 (1mM)
Incubation

LIT: Monoclonal antibodies to poly(adenosine diphosphate ribose) recognize
different structures: H. Kawamitsu, et al.; Biochemistry 23, 3771 (1984) (Original
Reference)  Detection of poly(ADP-ribose) polymerase and its reaction product poly(ADP-ribose) by immunocytochemistry: J.H. Küpper, et al.; Histochem.
J. 28, 391 (1996)  Multiparametric staining to identify apoptotic human cells: C.
Negri, et al.; Exp. Cell Res. 234, 174 (1997)  Poly(ADP-ribose) immunostaining todetect apoptosis induced by a neurotoxic fragment of prion protein: A. Bürkle, etal.; Histochem. J. 31, 711 (1999)  Reactive oxygen species participate in mdr1b
mRNA and P-glycoprotein overexpression in primary rat hepatocyte cultures: C.
Ziemann, et al.; Carcinogenesis 20, 407 (1999)  Detection of poly(ADP-ribose)synthesis in Drosophila testes upon gamma-irradiation: S. Lankenau, et al.; Chromosoma 108, 44 (1999)  Quantitative nonisotopic immuno-dot-blot method
for the assessment of cellular poly(ADP-ribosyl)ation capacity: R. Pfeiffer, et al.;Anal. Biochem. 275, 118 (1999)  Poly(ADP-ribosyl)ation, genomic instability,
and longevity: A. Bürkle; Ann. N. Y. Acad. Sci. 908, 126 (2000)  Flow-cytometricassessment of cellular poly(ADP-ribosyl)ation capacity in peripheral blood lymphocytes: A. Kunzmann, et al.; Immun. Ageing 3, 8 (2006)  For a comprehensive bibliography please visit our website.

Control

FIGURE: Detection of DNA damage.

MAb 10H

DAPI Staining

Apoptosis
Induction

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ALEXIS CORPORATION
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Control

FIGURE: HeLa irradiated cells with a microbeam laser.
Picture courtesy of C. Spenlehauer & G. de Murcia (CNRS, Strasbourg)

FIGURE: Detection of apoptotic cells by
immunofluorescence.

DNA Damage Marker
PAb to Histone γ-H2AX (human)(phosphorylated) (pSer139)
0 Gy

BENELUX
10P’s AXXORA BVBA
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10 Gy
Western blot
3T3 cells

20Gy -

LIT: Local DNA damage by proton microbeam irradiation induces poly(ADPribose) synthesis in mammalian cells: L. Tartier, et al.; Mutagenesis 18, 411(2003)+-+
γ-H2AX
Actin

laser microbeam

FIGURE: Detection of DNA damage induced globally (Xray irradiation with 10 Gray) or locally (laser microbeam irradiation) with anti-γ-H2AX PAb (Prod. No. ALX-210-390).
Picture courtesy of C. Spenlehauer & G. de Murcia (CNRS, Strasbourg).
FIGURE: Detection of DNA damage in HeLa cells induced locally with
anti-γ-H2AX PAb (Prod. No. ALX-210-390). Right) merged image ofanti-γ-H2AX PAb and HOE 33258 (Prod. No. ALX-620-051) staining.
Pictures courtesy of C. Spenlehauer & G. de Murcia (CNRS, Strasbourg).

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15-May-08

ALX-210-390-R050
50 μl
From rabbit. IMMUNOGEN: Synthetic peptide corresponding to Ser139-phosphorylated human γ-histone
H2AX (K134ATQApSQEY142). SPECIFICITY: Recognizes
Ser139-phosphorylated human H2AX. Does not crossreact with non-phosphorylated human H2AX. APPLICATION: ICC, WB.

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