Lysine Dendrons

Published on 02.12.2016

We now offer a series of Lysine dendrons for chemoselective functionalization of molecules containing carbonyl groups. These multivalent molecules carry diverse types of moieties, such as amine- or hydroxyl-groups, DOTA chelators or triphenylphosphonium (TPP) cations.

Dendronization is a synthetic method by which functional materials with specific architectures and useful new properties can be created.

We now offer several lysine dendrons equipped with a hydrazide functional group at the focal point/C-terminus for chemoselective conjugation to molecules bearing carbonyl groups. The conjugation can be performed with (or without) subsequent reduction of the hydrazone bond by NaBH4.

For your convenience, we offer a selection of Lys dendrons with spacer arms of different lengths (LS-3610, LS-3620, LS-3630). The terminal lysine residues can be further functionalized with amino-reactive molecules.

Moreover, we also offer a lysine dendron bearing several serine residues (LS-3640). By selective conjugation of this building block to peptides or polymers using the hydrazone ligation technique, multiple Ser residues can be incorporated into the target molecule, thus multiplying the number of reactive functional groups. Furthermore, these Ser residues can be converted to glyoxylic acid by periodate oxidation with NaIO4, thus creating multiple attachment sites for payloads with aldehyde-reactive groups.

Dendron and Dendrimer structure.

A further variant of our new dendrons is a DOTA-functionalized derivative (LS-3600). Conjugation of this dendron to peptide or polymer carrier molecules facilitates delivery of paramagnetic ions (Gd3+; Mn2+) or radioactive isotopes. Applications include the targeted delivery of MR contrast agents (e.g. Gd3+) and radioimmunotherapy.

Lastly, we included a triphenylphosphonium (TPP)-bearing dendron into our portfolio (LS-3650). This type of building block was designed for the targeted delivery of peptides, polymers and different drugs to mitochondria.

Our new dendrons (in the form of hydrazides) can be applied for the modification of synthetic or natural polymers containing reactive aldehyde groups (peptides must first be modified by oxidation of Ser or Thr residues). The dendrons can for example be applied for the design of gene delivery systems or for modifying the surface properties of polymers. The conjugation process can be performed using the hydrazone ligation approach with (or without) subsequent reduction of the resulting hydrazone bond by NaBH4. We can provide all necessary protocols.

 

→ Would you like to synthesize your own custom hydrazide-bearing dendrons? Use our Hydrazone Resin for convenient access to these structures.

References:

  • A dendronized heparin-gadolinium polymer self-assembled into a nanoscale system as a potential magnetic resonance imaging contrast agent; C. Guo, L. Sun, W. She, N. Li, L. Jiang, K. Luo, Q. Gong and Z. Gu; Polymer Chemistry 2016; 7: 2531-2541. doi:10.1039/c6py00059b

  • Effect of the Conjugation Density of Triphenylphosphonium Cation on the Mitochondrial Targeting of Poly(amidoamine) Dendrimers; E. R. Bielski, Q. Zhong, M. Brown and S. R. P. da Rocha; Molecular pharmaceutics 2015; 12: 3043-3053. doi:10.1021/acs.molpharmaceut.5b00320

  • Mitochondrial targeting dendrimer allows efficient and safe gene delivery; X. Wang, N. Shao, Q. Zhang and Y. Cheng; Journal of Materials Chemistry B 2014; 2: 2546-2553. doi:10.1039/c3tb21348j

  • A hydrazide-anchored dendron scaffold for chemoselective ligation strategies; L. O'Donovan and P. A. De Bank; Organic & Biomolecular Chemistry 2014; 12: 7290-7296. doi:10.1039/c4ob00870g

  • Peptide targeted tripod macrocyclic Gd(III) chelates for cancer molecular MRI; Z. Zhou, X. Wu, A. Kresak, M. Griswold and Z.-R. Lu; Biomaterials 2013; 34: 7683-7693. doi:http://dx.doi.org/10.1016/j.biomaterials.2013.06.057

  • Synthesis and Evaluation of a Peptide Targeted Small Molecular Gd-DOTA Monoamide Conjugate for MR Molecular Imaging of Prostate Cancer; X. Wu, S. M. Burden-Gulley, G.-P. Yu, M. Tan, D. Lindner, S. M. Brady-Kalnay and Z.-R. Lu; Bioconjugate Chemistry 2012; 23: 1548-1556. doi:10.1021/bc300009t

  • Dendronization: A Useful Synthetic Strategy to Prepare Multifunctional Materials; J. I. Paez, M. Martinelli, V. Brunetti and M. C. Strumia; Polymers 2012; 4: 355. 

  • Surface conjugation of triphenylphosphonium to target poly(amidoamine) dendrimers to mitochondria; S. Biswas, N. S. Dodwadkar, A. Piroyan and V. P. Torchilin; Biomaterials 2012; 33: 4773-4782. doi:http://dx.doi.org/10.1016/j.biomaterials.2012.03.032

  • Multiple Triphenylphosphonium Cations as a Platform for the Delivery of a Pro-Apoptotic Peptide; N. Kolevzon, U. Kuflik, M. Shmuel, S. Benhamron, I. Ringel and E. Yavin; Pharmaceutical Research 2011; 28: 2780. doi:10.1007/s11095-011-0494-6

  • MRI Detection of VEGFR2 in Vivo Using a Low Molecular Weight Peptoid−(Gd)8-Dendron for Targeting; L. M. De León-Rodríguez, A. Lubag, D. G. Udugamasooriya, B. Proneth, R. A. Brekken, X. Sun, T. Kodadek and A. Dean Sherry; Journal of the American Chemical Society 2010; 132: 12829-12831. doi:10.1021/ja105563a

  • Multiple Triphenylphosphonium Cations Shuttle a Hydrophilic Peptide into Mitochondria; S. E. Abu-Gosh, N. Kolvazon, B. Tirosh, I. Ringel and E. Yavin; Molecular pharmaceutics 2009; 6: 1138-1144. doi:10.1021/mp900032r

  • Inhibition of Mitosis by Glycopeptide Dendrimer Conjugates of Colchicine; D. Lagnoux, T. Darbre, M. L. Schmitz and J.-L. Reymond; Chemistry – A European Journal 2005; 11: 3941-3950. doi:10.1002/chem.200401294

  • Synthesis and Application of Peptide Dendrimers As Protein Mimetics; J. P. Tam and J. C. Spetzler; Current Protocols in Immunology 2001. doi:10.1002/0471142735.im0906s34

  • Assembly of cyclic peptide dendrimers from unprotected linear building blocks in aqueous solution; T. D. Pallin and J. P. Tam; Chemical Communications 1996: 1345-1346. doi:10.1039/cc9960001345