PEE-G dendrimers Apr17-2 · 10.1002/cmdc.201600270 10.1002/cmdc.201600270
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www.victoria.ac.nz/ferrier www.victoria.ac.nz/ferrier www.glycosyn.com http://dx.doi.org/doi:10.1002/cmdc.201600270 http://dx.doi.org/doi:10.1002/cmdc.201600270 http://dx.doi.org/doi:10.1002/cmdc.201600270 http://dx.doi.org/doi:10.1002/cmdc.201600270 http://dx.doi.org/doi:10.1002/cmdc.201600270 http://dx.doi.org/doi:10.1002/cmdc.201600270 http://dx.doi.org/doi:10.1002/cmdc.201600270 http://dx.doi.org/doi:10.1002/cmdc.201600270 http://dx.doi.org/doi:10.1002/cmdc.201600270 http://dx.doi.org/doi:10.1002/cmdc.201600270 http://dx.doi.org/doi:10.1002/cmdc.201600270 http://dx.doi.org/doi:10.1002/cmdc.201600270 http://dx.doi.org/doi:10.1002/cmdc.201600270 http://dx.doi.org/doi:10.1002/cmdc.201600270 http://dx.doi.org/doi:10.1002/cmdc.201600270 http://dx.doi.org/doi:10.1002/cmdc.201600270 http://dx.doi.org/doi:10.1002/cmdc.201600270 http://dx.doi.org/doi:10.1002/cmdc.201600270 http://dx.doi.org/doi:10.1002/cmdc.201600270 http://dx.doi.org/doi:10.1002/cmdc.201600270 http://dx.doi.org/doi:10.1002/cmdc.201600270 http://dx.doi.org/doi:10.1002/cmdc.201600270 15/2016 www.chemmedchem.org A J ournal of Cover Picture: P. M. Rendle et al. Poly Ethoxy Ethyl Glycinamide (PEE-G) Dendrimers: cally Designed for Pharmaceutical Applications Dendrimers are large, banched molecules with well-defined structure. They can be can be conjugated to or used to encapsulate therapeutic drugs or imaging moieties or may also be used as drugs in their own right. PEE-G dendrimers have been designed to be: Stable No observable degradation of G4 PEE-G CO 2 H after 24 hrs at 40 °C, neat or in PBS. Non-toxic Observed to have low cytotoxicity, low immunogenicity and acute tolerated dose in adult rats of >1000 mg/kg Pure High purity by HPLC and being constantly improved Scalable Made from cheap, readily available starting materials via an efficient, scalable, convergent synthesis Water soluble G4 PEE-G CO 2 H soluble in PBS at >400 mg/mL Flexible Long linkers between branching points giving a ‘low density’, long reach dendrimer Variations Free acid centre and/or free amine terminals. Carboxylic acid (mono or di) capped terminals. Alternating amine and hydroxy terminals. Our partners, GlycoSyn, have the ability to manufacture on kilogram scale and under GMP to provide products suitable for human clinical trials. PEE-G dendrimers can be purchased online: www.glycofinechem.glycosyn.com/collections/dendrimers The scaffold is patent protected and available for licensing. Contact Stephen Lorimer: [email protected]. Macromolecular scaffolds specifically designed for pharmaceutical applicatons PEE-G dendrimers O NHBoc O NHBoc O NHBoc O NHBoc O H N O N O N H O N NH O N O NH O O O BnO O NHBoc O NHBoc O NHBoc O NHBoc O H N O N O N H O N N O HN O N N O HN O O NHBoc O NHBoc O NHBoc O NHBoc O H N O N O N H O N O NHBoc O NHBoc O NHBoc O NHBoc O H N O N O N H O N N O HN O N N O HN O G4 BnO PEE-G NHBoc 4 6 8 10 12 14 16 18 20 0 10 20 30 40 50 98.6% 96.7% 94.4% 91.1% G1 HO PEE-G NHBoc G2 HO PEE-G NHBoc G3 HO PEE-G NHBoc Time / min G4 HO PEE-G NHBoc HPLC-CAD April 2017
Transcript of PEE-G dendrimers Apr17-2 · 10.1002/cmdc.201600270 10.1002/cmdc.201600270
www.victoria.ac.nz/ferrierwww.victoria.ac.nz/ferrier
www.glycosyn.com
http://dx.doi.org/doi:10.1002/cmdc.201600270http://dx.doi.org/doi:10.1002/cmdc.201600270http://dx.doi.org/doi:10.1002/cmdc.201600270http://dx.doi.org/doi:10.1002/cmdc.201600270http://dx.doi.org/doi:10.1002/cmdc.201600270http://dx.doi.org/doi:10.1002/cmdc.201600270http://dx.doi.org/doi:10.1002/cmdc.201600270http://dx.doi.org/doi:10.1002/cmdc.201600270http://dx.doi.org/doi:10.1002/cmdc.201600270http://dx.doi.org/doi:10.1002/cmdc.201600270http://dx.doi.org/doi:10.1002/cmdc.201600270http://dx.doi.org/doi:10.1002/cmdc.201600270http://dx.doi.org/doi:10.1002/cmdc.201600270http://dx.doi.org/doi:10.1002/cmdc.201600270http://dx.doi.org/doi:10.1002/cmdc.201600270http://dx.doi.org/doi:10.1002/cmdc.201600270http://dx.doi.org/doi:10.1002/cmdc.201600270http://dx.doi.org/doi:10.1002/cmdc.201600270http://dx.doi.org/doi:10.1002/cmdc.201600270http://dx.doi.org/doi:10.1002/cmdc.201600270http://dx.doi.org/doi:10.1002/cmdc.201600270http://dx.doi.org/doi:10.1002/cmdc.201600270
15/2016
www.chemmedchem.org
A J ournal ofCover Picture:P. M. Rendle et al.
Poly Ethoxy Ethyl Glycinamide (PEE-G) Dendrimers: cally Designed for Pharmaceutical Applications
Dendrimers are large, banched molecules with well-defined structure. They can be can be conjugated to or used to encapsulate therapeutic drugs or imaging moieties or may also be used as drugs in their own right.
PEE-G dendrimers have been designed to be:
Stable No observable degradation of G4 PEE-G CO2H after 24 hrs at 40 °C, neat or in PBS.
Non-toxic Observed to have low cytotoxicity, low immunogenicity and acute tolerated dose in adult rats of >1000 mg/kg
Pure High purity by HPLC and being constantly improved
Scalable Made from cheap, readily available starting materials via an efficient, scalable, convergent synthesis
Water soluble G4 PEE-G CO2H soluble in PBS at >400 mg/mL
Flexible Long linkers between branching points giving a ‘low density’, long reach dendrimer
Variations Free acid centre and/or free amine terminals. Carboxylic acid (mono or di) capped terminals. Alternating amine and hydroxy terminals.
Our partners, GlycoSyn, have the ability to manufacture on kilogram scale and under GMP to provide products suitable for human clinical trials.
PEE-G dendrimers can be purchased online:www.glycofinechem.glycosyn.com/collections/dendrimers
The scaffold is patent protected and available for licensing. Contact Stephen Lorimer: [email protected].
Macromolecular scaffolds specifically designed for pharmaceutical applicatons
PEE-G dendrimers
O NHBoc
O NHBocO NHBoc
O NHBoc
OHN
ON
O NH
ON
NH
O
N
O
NH
O
O
O
BnO
O NHBoc
O NHBocO
NHBocO
NHBoc
OHN
ON
O NH
ON
N
OHN
O
N
N
OHN
O
O NHBoc
O NHBocO NHBoc
O NHBoc
OHN
ON
O NH
ON
O NHBoc
O NHBocO NHBoc
O NHBoc
OHN
ON
O NH
ON
N
OHN
O
N
N
OHN
O
G4 BnO PEE-G NHBoc
4 6 8 10 12 14 16 18 200
10
20
30
40
50
98.6%
96.7%
94.4%
91.1%
G1 HO PEE-G NHBocG2 HO PEE-G NHBocG3 HO PEE-G NHBoc
Time / min
G4 HO PEE-G NHBoc
HPLC-CAD
April 2017
