Morpholino Amidates
ChemGenes is pleased to offer Exceptional Quality of Morpholino Phosphoramidate monomers for synthesis of Morpholino Phosphoramidate Oligomers (PMOs)
Introduction:
Phosphorodiamidate morpholinos (PMOs) are chemically modified oligonucleotides (ODNs) wherein the 2’-deoxyribonucleosides and phosphate linkages of canonical DNA are substituted with morpholino rings and phosphorodiamidate linkages respectively. They have been researched extensively inoligonucleotide therapeutics as potential steric blocking agents for the treatment of various genetic disorders. PMOs exhibit high hybridization affinity
to complementary RNA, possess excellent enzymatic stability both in vitro and in vivo and elicit low immunogenicity leading to acceptable toxicokinetic
profiles in mammalian models. The ability of PMOs to effectively function as steric blockers arises from their ability to specifically bind complementary
RNA both in vitro and in vivo.
Morpholinos block small (~25 base) regions of the base-pairing surfaces of ribonucleic acid (RNA). Morpholinos are six-membered rings which may
provide higher conformational rigidity when incorporated into an oligonucleotide (ODN) backbone.

B
AdenineCytosine
GuanineThymineProtection
N-Bz
N-Bz
N-iBu
N/A

Catalog#
ANP-3751
ANP-3752
ANP-3753
ANP-3754

Packing Size		
250mg, 500mg, 1g250mg, 500mg, 1g250mg, 500mg, 1g250mg, 500mg, 1g

Bulk quantities available : 10 g, 100 g, Please enquire.

Figure 1. Structure of Morpholino amidates

Figure. 2. UHPLC of G Morpholinophosphoramidate, Purity 100%

Fig. 3. 31P-NMR of G Morpholinophosphoramidate, purity100%

Toll Free: (800) 762-9323
33 Industrial Way, Wilmington, MA 01887 • T: (978) 694-4500 • F: (978) 694-4502

For more information, visit us at www.ChemGenes.com
1Morpholino Amidates
Application of Morpholino oligos and their therapeutic potentials:
Morpholino oligos are specific, soluble, non-toxic, stable, and effective antisense oligonucleotide suitable for development as therapeutics and currently in clinical trials. Efficacy of Morpholino oligos in humans has been shown in clinical trials for Duchenne muscular dystrophy. The splice modifying Morpholino eteplirsen has partially restored function to the dystrophin protein, enough to show significant
clinical benefit on a six-minute walk test versus the untreated control group.
Blocking translation- Morpholinos can bind to the 5’-untranslated region of messenger RNA (mRNA), and can interfere with progressionof the ribosomal initiation complex from the 5’ cap to the start codon.
Modifying pre-mRNA splicing- Morpholinos can prevent splice-directing small nuclear ribonucleoproteins (snRNP) complexes from binding introns of pre-mRNA, blocking the splice lariat structure, interfering with the binding of splice regulatory proteins such as splicesilencers[1] and splice enhancers [2] there by interfering with pre-mRNA processing steps.
Morpholinos can block miRNA activity [3][4] and maturation.[5] Fluorescein-tagged Morpholinos along with fluorescein-specific antibodies that could be used as probes for in-situ hybridization to miRNAs [6] Morpholinos can also block ribozyme activity .[7]Gene knockdown by morpholino- The morpholino-modified antisense oligonucleotides are primarily used in animal embryonic systems

Figure 4. The Synthesis of Morpholinophosphoramidate Oligonucleotides

for the ‘knock-down’ of gene function
Intron retention using RNA-targeting thiomorpholino antisense oligonucleotides.[8]References:1.

Stirchak, E. P., Summerton, J. E., & Weller, D. D. (1989). Uncharged stereoregular nucleic acid analogs: 2. Morpholino nucleoside oligomers with carbamate internucleoside linkages. Nucleic acids research, 17(15), 6129–6141. https://doi.org/10.1093/nar/17.15.6129

2.

Krishna, Heera; Jastrzebska, Katarzyna; Caruthers, Marvin, FEBS Letters, 17 June 2019, Volume593, Issue13 ,Krakow Special Issue Pages 1459-1467, https://doi.
org/10.1002/1873-3468.13492

3.

Bruno IG, Jin W, Cote GJ (October 2004). “Correction of aberrant FGFR1 alternative RNA splicing through targeting of intronic regulatory elements”. Human MolecularGenetics. 13(20): 2409–20. doi:10.1093/hmg/ddh272. PMID 15333583.

4.

Vetrini F, Tammaro R, Bondanza S, Surace EM, Auricchio A, De Luca M, Ballabio A, Marigo V (May 2006). “Aberrant splicing in the ocular albinism type 1 gene (OA1/GPR143) is corrected in vitro by morpholino antisense oligonucleotides”. Human Mutation. 27 (5): 420–6. doi:10.1002/humu.20303. PMID 16550551.

5.

Kloosterman WP, Wienholds E, Ketting RF, Plasterk RH (2004). “Substrate requirements for let-7 function in the developing zebrafish embryo”. Nucleic Acids Research.
32 (21): 6284–91. doi:10.1093/nar/gkh968. PMC 535676. PMID 15585662.

6.

Flynt AS, Li N, Thatcher EJ, Solnica-Krezel L, Patton JG (February 2007). “Zebrafish miR-214 modulates Hedgehog signaling to specify muscle cell fate”. Nature Genetics.
39 (2): 259–63. doi:10.1038/ng1953. PMC 3982799. PMID 17220889.

7.

Kloosterman WP, Lagendijk AK, Ketting RF, Moulton JD, Plasterk RH (August 2007). “Targeted inhibition of miRNA maturation with morpholinos reveals a role for miR-375
in pancreatic islet development”. PLOS Biology. 5 (8): e203. doi:10.1371/journal.pbio.0050203. PMC 1925136. PMID 17676975

8.

Lagendijk AK, Moulton JD, Bakkers J (June 2012). “Revealing details: whole mount microRNA in situ hybridization protocol for zebrafish embryos and adult tissues”.
Biology Open. 1 (6): 566–9. doi:10.1242/bio.2012810. PMC 3509442. PMID 23213449.

9.

Yen L, Svendsen J, Lee JS, Gray JT, Magnier M, Baba T, D’Amato RJ, Mulligan RC (September 2004). “Exogenous control of mammalian gene expression through modulation of RNA self-cleavage”. Nature. 431 (7007): 471–6. Bibcode:2004Natur.431..471Y. doi:10.1038/nature02844. PMID 15386015.

10. D. Gabrijela, B. Ulrich, K.Heera, J. Katarzyna, S. Michael, B. Benjamin, C.Thomas, C.Marvin, R.John Nuclear compartmentalization of TERT mRNA and TUG1 lncRNAtranscripts is driven by intron retention: implications for RNA-directed therapies.
11. K.Heera, J. Katarzyna, C. Marvin, P. Sibasish, V.Rakesh WO2019060522 - THIOMORPHOLINO OLIGONUCLEOTIDES FOR THE TREATMENT OF MUSCULAR DYSTROPHY.
12. Guide for Morpholino Users: Toward Therapeutics J Drug Discov Develop and Deliv. 2016; 3(2): 1023. Gene Tools, LLC, USA *Corresponding author: Moulton JD, GeneTools, LLC, 1001 Summerton Way, Philomath, Oregon 97370, USA.
*The subject products are available from ChemGenes Corp., thanks to a license agreement for Morpholino Oligonucleotide Synthesis Technology developed by University of Colorado, Boulder (10)(11).

ChemGenes Corporation is now ISO 9001:2008 Certified Company

For a complete product listing, visit us at www.chemgenes.com

2