skip to main content
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Synthesis and mechanistic investigations of pH-responsive cationic poly(aminoester)s

Abstract

The synthesis and degradation mechanisms of a class of pH-sensitive, rapidly degrading cationic poly(α-aminoester)s are described.

Authors:
ORCiD logo [1]; ORCiD logo [1];  [1];  [1];  [1];  [2]; ORCiD logo [1]
  1. Department of Chemistry, Stanford University, Stanford, USA
  2. Department of Chemistry, Stanford University, Stanford, USA, Department of Chemical and Systems Biology
Publication Date:
Sponsoring Org.:
USDOE
OSTI Identifier:
1600850
Grant/Contract Number:  
[SC0018168]
Resource Type:
Published Article
Journal Name:
Chemical Science
Additional Journal Information:
[Journal Name: Chemical Science Journal Volume: 11 Journal Issue: 11]; Journal ID: ISSN 2041-6520
Publisher:
Royal Society of Chemistry (RSC)
Country of Publication:
United Kingdom
Language:
English

Citation Formats

Blake, Timothy R., Ho, Wilson C., Turlington, Christopher R., Zang, Xiaoyu, Huttner, Melanie A., Wender, Paul A., and Waymouth, Robert M. Synthesis and mechanistic investigations of pH-responsive cationic poly(aminoester)s. United Kingdom: N. p., 2020. Web. doi:10.1039/C9SC05267D.
Blake, Timothy R., Ho, Wilson C., Turlington, Christopher R., Zang, Xiaoyu, Huttner, Melanie A., Wender, Paul A., & Waymouth, Robert M. Synthesis and mechanistic investigations of pH-responsive cationic poly(aminoester)s. United Kingdom. doi:10.1039/C9SC05267D.
Blake, Timothy R., Ho, Wilson C., Turlington, Christopher R., Zang, Xiaoyu, Huttner, Melanie A., Wender, Paul A., and Waymouth, Robert M. Wed . "Synthesis and mechanistic investigations of pH-responsive cationic poly(aminoester)s". United Kingdom. doi:10.1039/C9SC05267D.
@article{osti_1600850,
title = {Synthesis and mechanistic investigations of pH-responsive cationic poly(aminoester)s},
author = {Blake, Timothy R. and Ho, Wilson C. and Turlington, Christopher R. and Zang, Xiaoyu and Huttner, Melanie A. and Wender, Paul A. and Waymouth, Robert M.},
abstractNote = {The synthesis and degradation mechanisms of a class of pH-sensitive, rapidly degrading cationic poly(α-aminoester)s are described.},
doi = {10.1039/C9SC05267D},
journal = {Chemical Science},
number = [11],
volume = [11],
place = {United Kingdom},
year = {2020},
month = {3}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
DOI: 10.1039/C9SC05267D

Save / Share:

Works referenced in this record:

mRNA vaccination with charge-altering releasable transporters elicits human T cell responses and cures established tumors in mice
journal, September 2018

  • Haabeth, Ole A. W.; Blake, Timothy R.; McKinlay, Colin J.
  • Proceedings of the National Academy of Sciences, Vol. 115, Issue 39
  • DOI: 10.1073/pnas.1810002115

Fluorous Comonomer Modulates the Reactivity of Cyclic Ketene Acetal and Degradation of Vinyl Polymers
journal, November 2017


A Cascade Biodegradable Polymer Based on Alternating Cyclization and Elimination Reactions
journal, December 2009

  • DeWit, Matthew A.; Gillies, Elizabeth R.
  • Journal of the American Chemical Society, Vol. 131, Issue 51
  • DOI: 10.1021/ja905343x

Acetals as pH-Sensitive Linkages for Drug Delivery
journal, November 2004

  • Gillies, Elizabeth R.; Goodwin, Andrew P.; Fréchet, Jean M. J.
  • Bioconjugate Chemistry, Vol. 15, Issue 6, p. 1254-1263
  • DOI: 10.1021/bc049853x

Intramolecular Reaction between Neighboring Substituents of Vinyl Polymers
journal, June 1939

  • Flory, Paul J.
  • Journal of the American Chemical Society, Vol. 61, Issue 6
  • DOI: 10.1021/ja01875a053

Enhanced mRNA delivery into lymphocytes enabled by lipid-varied libraries of charge-altering releasable transporters
journal, June 2018

  • McKinlay, Colin J.; Benner, Nancy L.; Haabeth, Ole A.
  • Proceedings of the National Academy of Sciences, Vol. 115, Issue 26
  • DOI: 10.1073/pnas.1805358115

Aliphatic polyesters for medical imaging and theranostic applications
journal, November 2015

  • Nottelet, Benjamin; Darcos, Vincent; Coudane, Jean
  • European Journal of Pharmaceutics and Biopharmaceutics, Vol. 97
  • DOI: 10.1016/j.ejpb.2015.06.023

A reduction sensitive cascade biodegradable linear polymer
journal, August 2010

  • Dewit, Matthew A.; Beaton, Annelise; Gillies, Elizabeth R.
  • Journal of Polymer Science Part A: Polymer Chemistry, Vol. 48, Issue 18
  • DOI: 10.1002/pola.24180

Lipid Nanoparticle Assisted mRNA Delivery for Potent Cancer Immunotherapy
journal, December 2016


In vivo fate tracking of degradable nanoparticles for lung gene transfer using PET and Ĉerenkov imaging
journal, August 2016


Intramolecular Cyclization for Stimuli-Controlled Depolymerization of Polycaprolactone Particles Leading to Disassembly and Payload Release
journal, April 2013

  • de Gracia Lux, Caroline; Almutairi, Adah
  • ACS Macro Letters, Vol. 2, Issue 5
  • DOI: 10.1021/mz400129h

Light-Triggered Intramolecular Cyclization in Poly(lactic- co -glycolic acid)-Based Polymers for Controlled Degradation
journal, May 2015


Self-Immolative Spacers: Kinetic Aspects, Structure-Property Relationships, and Applications
journal, June 2015

  • Alouane, Ahmed; Labruère, Raphaël; Le Saux, Thomas
  • Angewandte Chemie International Edition, Vol. 54, Issue 26
  • DOI: 10.1002/anie.201500088

Synthesis and Structure Determination of (3S, 5S)-2,3,5,6-Tetrahydro-3,5-dialkyl-N-(tert-butyloxycarbonyl)-4H-1,4-oxazine-2-ones
journal, March 1992


Transmission of substituent effects in polar reactions. Part 1.—Field effects in ester hydrolysis
journal, January 1971


pH-Sensitive Polymers as Dynamic Mediators of Barriers to Nucleic Acid Delivery
journal, November 2018


Self-Immolative Polymers
journal, April 2008

  • Sagi, Amit; Weinstain, Roy; Karton, Naama
  • Journal of the American Chemical Society, Vol. 130, Issue 16
  • DOI: 10.1021/ja801065d

Exact stochastic simulation of coupled chemical reactions
journal, December 1977

  • Gillespie, Daniel T.
  • The Journal of Physical Chemistry, Vol. 81, Issue 25
  • DOI: 10.1021/j100540a008

Self-immolative nanoparticles for simultaneous delivery of microRNA and targeting of polyamine metabolism in combination cancer therapy
journal, January 2017


Degradable Poly(β-amino esters):  Synthesis, Characterization, and Self-Assembly with Plasmid DNA
journal, November 2000

  • Lynn, David M.; Langer, Robert
  • Journal of the American Chemical Society, Vol. 122, Issue 44
  • DOI: 10.1021/ja0015388

2,5-Diketopiperazines: Synthesis, Reactions, Medicinal Chemistry, and Bioactive Natural Products
journal, April 2012


Organocatalytic Ring-Opening Polymerization
journal, December 2007

  • Kamber, Nahrain E.; Jeong, Wonhee; Waymouth, Robert M.
  • Chemical Reviews, Vol. 107, Issue 12
  • DOI: 10.1021/cr068415b

The kinetics of acid hydrolysis of dipeptides
journal, January 1956

  • Harris, J. I.; Cole, R. D.; Pon, N. G.
  • Biochemical Journal, Vol. 62, Issue 1
  • DOI: 10.1042/bj0620154

Preparation of poly(L-serine ester): a structural analog of conventional poly(L-serine)
journal, July 1990


Materials for non-viral intracellular delivery of messenger RNA therapeutics
journal, October 2016


Switchable polymer-grafted mesoporous silica's: from polyesters to polyamides biosilica hybrid materials
journal, September 2013


Kinetics of Self-Immolative Degradation in a Linear Polymeric System: Demonstrating the Effect of Chain Length
journal, June 2013

  • McBride, Ryan A.; Gillies, Elizabeth R.
  • Macromolecules, Vol. 46, Issue 13
  • DOI: 10.1021/ma4009753

Kinetics of the Reactions of O-Acetylethanolamine.
journal, January 1963


Triggered degradation of poly(ester amide)s via cyclization of pendant functional groups of amino acid monomers
journal, January 2013

  • Mejia, José S.; Gillies, Elizabeth R.
  • Polymer Chemistry, Vol. 4, Issue 6
  • DOI: 10.1039/c3py21094d

Hydroxy-group participation in ester hydrolysis
journal, January 1973

  • Capon, Brian; McDowell, Samuel T.; Raftery, William V.
  • Journal of the Chemical Society, Perkin Transactions 2, Issue 8
  • DOI: 10.1039/p29730001118

Polyphosphoramidates That Undergo Acid-Triggered Backbone Degradation
journal, February 2017


The uncatalysed and copper(II) promoted hydrolysis of 4-nitrophenyl glycinate
journal, January 1986

  • Hay, Robert W.; Basak, Arup K.
  • Journal of the Chemical Society, Dalton Transactions, Issue 1
  • DOI: 10.1039/dt9860000039

UV and Near-IR Triggered Release from Polymeric Nanoparticles
journal, July 2010

  • Fomina, Nadezda; McFearin, Cathryn; Sermsakdi, Marleen
  • Journal of the American Chemical Society, Vol. 132, Issue 28
  • DOI: 10.1021/ja102595j

Specificity of bond fission during the acid hydrolysis of insulin
journal, February 1954


Functional DNA Delivery Enabled by Lipid-Modified Charge-Altering Releasable Transporters (CARTs)
journal, May 2018


Local Delivery of Ox40l , Cd80 , and Cd86 mRNA Kindles Global Anticancer Immunity
journal, January 2019


Intramolecular aminolysis of esters. O-Acetylserine and .gamma.-esters of glutamic acid
journal, April 1981

  • Caswell, Michael; Chaturvedi, Rama K.; Lane, Stuart M.
  • The Journal of Organic Chemistry, Vol. 46, Issue 8
  • DOI: 10.1021/jo00321a011

Self-immolative chemistry in nanomedicine
journal, May 2018


Polyglyoxylamides: Tuning Structure and Properties of Self-Immolative Polymers
journal, December 2018


Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis
journal, July 2018

  • Adams, David; Gonzalez-Duarte, Alejandra; O’Riordan, William D.
  • New England Journal of Medicine, Vol. 379, Issue 1
  • DOI: 10.1056/NEJMoa1716153

Amino Acid Esters of Phenols as Prodrugs: Synthesis and Stability of Glycine, β-Aspartic acid, and α-Aspartic Acid Esters of p-Acetamidophenol
journal, August 1981

  • Kovach, Ildiko M.; Pitman, Ian H.; Higuchi, Takeru
  • Journal of Pharmaceutical Sciences, Vol. 70, Issue 8
  • DOI: 10.1002/jps.2600700812

Charge-altering releasable transporters (CARTs) for the delivery and release of mRNA in living animals
journal, January 2017

  • McKinlay, Colin J.; Vargas, Jessica R.; Blake, Timothy R.
  • Proceedings of the National Academy of Sciences, Vol. 114, Issue 4
  • DOI: 10.1073/pnas.1614193114

mRNA Delivery System for Targeting Antigen-Presenting Cells In Vivo
journal, June 2018

  • Fornaguera, Cristina; Guerra-Rebollo, Marta; Ángel Lázaro, Miguel
  • Advanced Healthcare Materials, Vol. 7, Issue 17
  • DOI: 10.1002/adhm.201800335

Aliphatic Polyester Block Polymer Design
journal, March 2016


Proton ionisation constants and kinetics of base hydrolysis of some α-amino-acid esters in aqueous solution
journal, January 1967


Competitive intramolecular aminolysis: Relative rates of 5- and 6-membered lactam ring closure
journal, January 1994


Kinetics of the acid and alkaline hydrolysis of ethoxycarbonylmethyltriethylammonium chloride
journal, January 1954


The basic hydrolysis of amino acid esters
journal, January 1966

  • Hay, Rw; Porter, Lj; Morris, Pj
  • Australian Journal of Chemistry, Vol. 19, Issue 7
  • DOI: 10.1071/CH9661197

Nanotechnologies in delivery of mRNA therapeutics using nonviral vector-based delivery systems
journal, January 2017


Hydrogen-bonding organocatalysts for ring-opening polymerization
journal, January 2014


Ultrafast in situ forming poly(ethylene glycol)-poly(amido amine) hydrogels with tunable drug release properties via controllable degradation rates
journal, June 2019

  • Buwalda, Sytze J.; Bethry, Audrey; Hunger, Sylvie
  • European Journal of Pharmaceutics and Biopharmaceutics, Vol. 139
  • DOI: 10.1016/j.ejpb.2019.04.006

Oligo(serine ester) Charge-Altering Releasable Transporters: Organocatalytic Ring-Opening Polymerization and their Use for in Vitro and in Vivo mRNA Delivery
journal, May 2019

  • Benner, Nancy L.; McClellan, Rebecca L.; Turlington, Christopher R.
  • Journal of the American Chemical Society, Vol. 141, Issue 21
  • DOI: 10.1021/jacs.9b03154

Acid-Triggered, Acid-Generating, and Self-Amplifying Degradable Polymers
journal, January 2019

  • Miller, Kali A.; Morado, Ephraim G.; Samanta, Shampa R.
  • Journal of the American Chemical Society, Vol. 141, Issue 7
  • DOI: 10.1021/jacs.8b07705

Self-propagating amplification reactions for molecular detection and signal amplification: Advantages, pitfalls, and challenges
journal, March 2018

  • Sun, Xiaolong; Shabat, Doron; Phillips, Scott T.
  • Journal of Physical Organic Chemistry, Vol. 31, Issue 8
  • DOI: 10.1002/poc.3827

Continuous Head-to-Tail Depolymerization: An Emerging Concept for Imparting Amplified Responses to Stimuli-Responsive Materials
journal, March 2014

  • Phillips, Scott T.; DiLauro, Anthony M.
  • ACS Macro Letters, Vol. 3, Issue 4
  • DOI: 10.1021/mz5000784

From Polyesters to Polyamides Via ON Acyl Migration: An Original Multi-Transfer Reaction
journal, May 2011

  • Tailhades, Julien; Blanquer, Sébastien; Nottelet, Benjamin
  • Macromolecular Rapid Communications, Vol. 32, Issue 12
  • DOI: 10.1002/marc.201100235

Dendritic, Oligomeric, and Polymeric Self-Immolative Molecular Amplification
journal, September 2015


Amine-Functionalized Polylactide–PEG Copolymers
journal, April 2018


Effects of neighboring sulfides and pH on ester hydrolysis in thiol–acrylate photopolymers
journal, July 2007


Organocatalytic Ring-Opening Polymerization of Morpholinones: New Strategies to Functionalized Polyesters
journal, June 2014

  • Blake, Timothy R.; Waymouth, Robert M.
  • Journal of the American Chemical Society, Vol. 136, Issue 26
  • DOI: 10.1021/ja503830c

Antimicrobial activity of betaine esters, quaternary ammonium amphiphiles which spontaneously hydrolyze into nontoxic components.
journal, October 1990

  • Lindstedt, M.; Allenmark, S.; Thompson, R. A.
  • Antimicrobial Agents and Chemotherapy, Vol. 34, Issue 10
  • DOI: 10.1128/AAC.34.10.1949

Synthetic materials at the forefront of gene delivery
journal, September 2018


Easy synthesis and ring-opening polymerization of 5-Z-amino-δ-valerolactone: New degradable amino-functionalized (Co)polyesters
journal, November 2010

  • Blanquer, Sebastien; Tailhades, Julien; Darcos, Vincent
  • Journal of Polymer Science Part A: Polymer Chemistry, Vol. 48, Issue 24
  • DOI: 10.1002/pola.24400

Role of Quinones in Toxicology
journal, March 2000

  • Bolton, Judy L.; Trush, Michael A.; Penning, Trevor M.
  • Chemical Research in Toxicology, Vol. 13, Issue 3
  • DOI: 10.1021/tx9902082

Development of a Safe Gene Delivery System Using Biodegradable Polymer, Poly[α-(4-aminobutyl)- l -glycolic acid]
journal, July 2000

  • Lim, Yong-beom; Kim, Chang-hwan; Kim, Kwan
  • Journal of the American Chemical Society, Vol. 122, Issue 27
  • DOI: 10.1021/ja001033h

A Self-Destroying Polycationic Polymer:  Biodegradable Poly(4-hydroxy- l -proline ester)
journal, June 1999

  • Lim, Yong-beom; Choi, Young Hun; Park, Jong-sang
  • Journal of the American Chemical Society, Vol. 121, Issue 24
  • DOI: 10.1021/ja984012k

Polymer-Lipid Nanoparticles for Systemic Delivery of mRNA to the Lungs
journal, September 2016

  • Kaczmarek, James C.; Patel, Asha K.; Kauffman, Kevin J.
  • Angewandte Chemie International Edition, Vol. 55, Issue 44
  • DOI: 10.1002/anie.201608450

Smart Biomaterials: Recent Advances and Future Directions
journal, September 2018

  • Kowalski, Piotr S.; Bhattacharya, Chandrabali; Afewerki, Samson
  • ACS Biomaterials Science & Engineering, Vol. 4, Issue 11
  • DOI: 10.1021/acsbiomaterials.8b00889

Synthesis of functional polyesters derived from serine
journal, October 1990

  • Fiétier, Isabelle; Le Borgne, Alain; Spassky, Nicolas
  • Polymer Bulletin, Vol. 24, Issue 4
  • DOI: 10.1007/BF00294086

Amplified release through the stimulus triggered degradation of self-immolative oligomers, dendrimers, and linear polymers
journal, August 2012

  • Wong, Andrew D.; DeWit, Matthew A.; Gillies, Elizabeth R.
  • Advanced Drug Delivery Reviews, Vol. 64, Issue 11
  • DOI: 10.1016/j.addr.2011.09.012

A study of the partial acid hydrolysis of some proteins, with special reference to the mode of linkage of the basic amino-acids
journal, December 1941

  • Gordon, A. H.; Martin, A. J. P.; Synge, R. L. M.
  • Biochemical Journal, Vol. 35, Issue 12
  • DOI: 10.1042/bj0351369

Designing Smart Polymer Conjugates for Controlled Release of Payloads
journal, February 2018


Self-Immolative Poly(4,5-dichlorophthalaldehyde) and its Applications in Multi-Stimuli-Responsive Macroscopic Plastics
journal, March 2015

  • DiLauro, Anthony M.; Lewis, Gregory G.; Phillips, Scott T.
  • Angewandte Chemie International Edition, Vol. 54, Issue 21
  • DOI: 10.1002/anie.201501320

Efficient and Selective Cu/Nitroxyl-Catalyzed Methods for Aerobic Oxidative Lactonization of Diols
journal, March 2015

  • Xie, Xiaomin; Stahl, Shannon S.
  • Journal of the American Chemical Society, Vol. 137, Issue 11
  • DOI: 10.1021/jacs.5b01036

Progress towards the Synthesis of Amino Polyesters via Ring-Opening Polymerization (ROP) of Functional Lactones
journal, July 2016


Intramolecular cyclization assistance for fast degradation of ornithine-based poly(ester amide)s
journal, June 2013

  • de Gracia Lux, Caroline; Olejniczak, Jason; Fomina, Nadezda
  • Journal of Polymer Science Part A: Polymer Chemistry, Vol. 51, Issue 18
  • DOI: 10.1002/pola.26788

Quantitative Ring-Closing Metathesis of Polyolefins
journal, January 1996

  • Coates, Geoffrey W.; Grubbs, Robert H.
  • Journal of the American Chemical Society, Vol. 118, Issue 1
  • DOI: 10.1021/ja9532603

Depolymerizable poly(benzyl ether)-based materials for selective room temperature recycling
journal, January 2015

  • Baker, Matthew S.; Kim, Hyungwoo; Olah, Michael G.
  • Green Chemistry, Vol. 17, Issue 9
  • DOI: 10.1039/C5GC01090J