The use of maleic anhydride for the reversible blocking of amino groups on polypeptide chains

1. Maleic anhydride was shown to react rapidly and specifically with amino groups of proteins and peptides. Complete substitution of chymotrypsinogen was achieved under mild conditions and the extent of reaction could be readily determined from the spectrum of the maleyl-protein. 2. Maleyl-proteins are generally soluble and disaggregated at neutral pH. Trypsin splits the blocked proteins only at arginine residues and there is frequently selectivity in this cleavage, e.g. in yeast alcohol dehydrogenase and pig glyceraldehyde 3-phosphate dehydrogenase. 3. The group is removed by intramolecular catalysis at acid pH. The half-time was 11–12hr. at 37° at pH3·5 in ∈-maleyl-lysine or in maleyl-chymotrypsinogen. 4. The unblocking reaction can be used as the basis for a ‘diagonal’-electrophoretic separation of lysine peptides and N-terminal peptides, as shown by studies with β-melanocyte-stimulating hormone.

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Crystallization of liver alcohol dehydrogenase activated by the modification of amino groups

Journal of Molecular Biology ◽

10.1016/0022-2836(78)90225-5 ◽

1978 ◽

Vol 119 (3) ◽

pp. 451-453 ◽

Cited By ~ 7

Author(s):

Bryce V. Plapp ◽

Eila Zeppezauer ◽

Carl-Ivar Brändén

Keyword(s):

Alcohol Dehydrogenase ◽

Amino Groups ◽

Liver Alcohol Dehydrogenase

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Sericin cocoon bio-compatibilizer for reactive blending of thermoplastic cassava starch

Scientific Reports ◽

10.1038/s41598-021-99417-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Thanongsak Chaiyaso ◽

Pornchai Rachtanapun ◽

Nanthicha Thajai ◽

Krittameth Kiattipornpithak ◽

Pensak Jantrawut ◽

...

Keyword(s):

Mechanical Properties ◽

Maleic Anhydride ◽

Crystal Size ◽

Thermoplastic Starch ◽

Cassava Starch ◽

Chain Extension ◽

Amino Groups ◽

Reactive Blending ◽

Elongation At Break ◽

Small Crystal Size

AbstractCassava starch was blended with glycerol to prepare thermoplastic starch (TPS). Thermoplastic starch was premixed with sericin (TPSS) by solution mixing and then melt-blended with polyethylene grafted maleic anhydride (PEMAH). The effect of sericin on the mechanical properties, morphology, thermal properties, rheology, and reaction mechanism was investigated. The tensile strength and elongation at break of the TPSS10/PEMAH blend were improved to 12.2 MPa and 100.4%, respectively. The TPS/PEMAH morphology presented polyethylene grafted maleic anhydride particles (2 μm) dispersed in the thermoplastic starch matrix, which decreased in size to approximately 200 nm when 5% sericin was used. The melting temperature of polyethylene grafted maleic anhydride (121 °C) decreased to 111 °C because of the small crystal size of the polyethylene grafted maleic anhydride phase. The viscosity of TPS/PEMAH increased with increasing sericin content because of the chain extension. Fourier-transform infrared spectroscopy confirmed the reaction between the amino groups of sericin and the maleic anhydride groups of polyethylene grafted maleic anhydride. This reaction reduced the interfacial tension between thermoplastic starch and polyethylene grafted maleic anhydride, which improved the compatibility, mechanical properties, and morphology of the blend.

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Topological Aspects of the Design of Nanocarriers for Therapeutic Peptides and Proteins

Pharmaceutics ◽

10.3390/pharmaceutics11020091 ◽

2019 ◽

Vol 11 (2) ◽

pp. 91 ◽

Cited By ~ 10

Author(s):

Nadezhda Knauer ◽

Ekaterina Pashkina ◽

Evgeny Apartsin

Keyword(s):

Protein Delivery ◽

Topological Type ◽

Target Tissue ◽

Administration Route ◽

Topological Groups ◽

Advantages And Disadvantages ◽

Therapeutic Peptides ◽

Polypeptide Chains ◽

Careful Design ◽

Proteins And Peptides

Supramolecular chemistry holds great potential for the design of versatile and safe carriers for therapeutic proteins and peptides. Nanocarriers can be designed to meet specific criteria for given application (exact drug, administration route, target tissue, etc.). However, alterations in the topology of formulation components can drastically change their activity. This is why the supramolecular topology of therapeutic nanoconstructions has to be considered. Herein, we discuss several topological groups used for the design of nanoformulations for peptide and protein delivery: modification of polypeptide chains by host-guest interactions; packaging of proteins and peptides into liposomes; complexation and conjugation with dendrimers. Each topological type has its own advantages and disadvantages, so careful design of nanoformulations is needed. Ideally, each case where nanomedicine is needed requires a therapeutic construction specially created for that taking into account features of the administration route, target tissue, or organ, properties of a drug, its bioavailability, etc. The wide number of studies in the field of protein delivery by supramolecular and nanocarriers for proteins and peptides evidence their increasing potential for different aspects of the innovative medicine. Although significant progress has been achieved in the field, there are several remaining challenges to be overcome in future.

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Effect of Maleylation and Amidination of Hemoglobin on its Haptoglobin and Oxygen Reactions

Canadian Journal of Biochemistry ◽

10.1139/o71-021 ◽

1971 ◽

Vol 49 (2) ◽

pp. 148-153 ◽

Cited By ~ 5

Author(s):

W. L. Lockhart ◽

David B. Smith

Keyword(s):

Maleic Anhydride ◽

Sedimentation Rate ◽

Gel Filtration ◽

Bohr Effect ◽

Human Hemoglobin ◽

Amino Groups ◽

Structural Alterations ◽

Cooperative Effects ◽

Oxygen Equilibrium

Maleic anhydride and ethyl acetimidate reacted readily with all ε-amino groups of human hemoglobin. Maleyl-hemoglobin showed evidence of structural alterations and did not bind to haptoglobin. Amidino-hemoglobin was similar to hemoglobin in electrophoresis below pH 9, sedimentation rate, and gel filtration. Its oxygen equilibrium showed no cooperative effects or Bohr effect. Since it retained capacity to bind haptoglobin, it is concluded that hemoglobin amino groups are not involved in the reaction with haptoglobin.

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The reaction of aldolase with 2-methylmaleic anhydride

Biochemical Journal ◽

10.1042/bj1160843 ◽

1970 ◽

Vol 116 (5) ◽

pp. 843-849 ◽

Cited By ~ 93

Author(s):

I. Gibbons ◽

R. N. Perham

Keyword(s):

Enzyme Activity ◽

Maleic Anhydride ◽

Enzymic Activity ◽

Side Reactions ◽

Rabbit Muscle ◽

Thiol Groups ◽

Amino Groups ◽

Partial Loss ◽

Reaction Proceeds ◽

Citraconic Anhydride

1. The reaction of rabbit muscle aldolase with 2-methylmaleic anhydride is described. All the protein amino groups can be reversibly blocked. 2. As the reaction proceeds, the enzyme activity decreases until, at about 50% citraconylation of amino groups, the enzyme is completely inhibited. At this stage, little or no dissociation of the enzyme tetramer is observed and 75% of the activity is recoverable on unblocking the amino groups. 3. At 80% blocking, the enzyme is completely dissociated but little enzymic activity is recoverable after unblocking. Inability to recover activity after citraconylation and unblocking correlates with the onset of dissociation of the citraconyl-aldolase seen on ultracentrifugation. 4. The only irreversible modification of the enzyme primary structure detectable after the citraconylation and unblocking reactions is the partial loss of thiol groups. It is probable that this is responsible for the inability to reform active enzyme from the citraconylated subunit. 5. Other reversible side reactions of maleic anhydride and citraconic anhydride that may occur with proteins are discussed.

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Sericin cocoon bio-compatibilizer for reactive blending of thermoplastic cassava starch

10.21203/rs.3.rs-701614/v1 ◽

2021 ◽

Author(s):

Thanongsak Chaiyaso ◽

Pornchai Rachtanapun ◽

Nanthicha Thajai ◽

Krittameth kiattipronpithak ◽

Pensak Jantrawut ◽

...

Keyword(s):

Mechanical Properties ◽

Maleic Anhydride ◽

Crystal Size ◽

Thermoplastic Starch ◽

Cassava Starch ◽

Chain Extension ◽

Amino Groups ◽

Reactive Blending ◽

Elongation At Break ◽

Small Crystal Size

Abstract Cassava starch was blended with glycerol to prepare thermoplastic starch (TPS). TPS was premixed with sericin (TPSS) by solution mixing and then melt-blended with polyethylene grafted maleic anhydride (PEMAH). The effect of sericin on the mechanical properties, morphology, thermal properties, rheology, and reaction mechanism was investigated. The tensile strength and elongation at break of the TPSS10/PEMAH blend were improved to 12.2 MPa and 100.4%, respectively. The TPS/PEMAH morphology presented PEMAH particles (2 µm) dispersed in the TPS matrix, which decreased in size to approximately 200 nm when 5% sericin was used. The melting temperature of PEMAH (121°C) decreased to 111°C because of the small crystal size of the PEMAH phase. The viscosity of TPS/PEMAH increased with increasing sericin content because of the chain extension. Fourier-transform infrared spectroscopy (FTIR) confirmed the reaction between the amino groups of sericin and the maleic anhydride groups of PEMAH. This reaction reduced the interfacial tension between TPS and PEMAH, which improved the compatibility, mechanical properties, and morphology of the blend.

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Effect of Pollyallylamine on Alcoholdehydrogenase Structure and Activity

Polymers ◽

10.3390/polym12040832 ◽

2020 ◽

Vol 12 (4) ◽

pp. 832

Author(s):

Aleksandr L. Kim ◽

Egor V. Musin ◽

Alexey V. Dubrovskii ◽

Sergey A. Tikhonenko

Keyword(s):

Alcohol Dehydrogenase ◽

Quaternary Structure ◽

Inhibitory Effect ◽

Affinity Constant ◽

Structure And Properties ◽

Amino Groups ◽

Sulfate Anion ◽

Polyelectrolyte Microcapsules ◽

Adh Activity ◽

Structure And Activity

In this article, the effect of polyallylamine (PAA) on the structure and catalytic characteristics of alcohol dehydrogenase (ADH) was studied. For this research, we used methods of stationary kinetics and fluorescence spectroscopy. It has been shown that PAA non-competitively inhibits ADH activity while preserving its quaternary structure. It was established that 0.1 M ammonium sulfate removes the inhibitory effect of PAA on ADH, which is explained by the binding of sulfate anion (NH4)2SO4 with polyallylamine amino groups. As a result, the rigidity of the polymer chain increases and the ability to bind to the active loop of the enzyme increases. It is also shown that sodium chloride removes the inhibitory effect of PAA on ADH due to an electrostatic screening of the enzyme from polyelectrolyte. The method of encapsulating ADH in polyelectrolyte microcapsules was adapted to the structure and properties of the enzyme molecule. It was found that the best for ADH is its encapsulation by adsorption into microcapsules already formed on CaCO3 particles. It was shown that the affinity constant of encapsulated alcohol dehydrogenase to the substrate is 1.7 times lower than that of the native enzyme. When studying the affinity constant of ADH in a complex with PAA to ethanol, the effect of noncompetitive inhibition of the enzyme by polyelectrolyte was observed.

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Dna-Binding Compounds. IV. Synthesis and Solution Conformation of a Novel Macrocyle Formed by Coupling of the Side-Chains of Adjacent L-Lysine Residues

Australian Journal of Chemistry ◽

10.1071/ch9911649 ◽

1991 ◽

Vol 44 (11) ◽

pp. 1649 ◽

Cited By ~ 2

Author(s):

AM Bray ◽

DP Kelly ◽

TK Lim

Keyword(s):

Carboxylic Acid ◽

Dimethyl Sulfoxide ◽

The Novel ◽

Two Dimensional ◽

Amino Groups ◽

Solution Conformation ◽

Mild Conditions ◽

Dimethyl Sulfoxide Solution ◽

Acid Methyl ◽

Lysine Residues

The novel macrocyclic dilysine derivatives (8S,11S)-11-t-butoxycarbonylamino-2,10-dioxo-1,3,9-triazacyclopentadecane-8-carboxylic acid methyl (5) and t-butyl (6) esters were prepared by coupling of the є-amino groups of adjacent lysine residues of the esters of Boc-Lys-Lys-OR with 1,1′-carbonyldiimidazole under mild conditions. The conformation of (6) in dimethyl sulfoxide solution was determined by the use of a variety of one- and two-dimensional n.m.r. techniques.

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An amine protecting group deprotectable under nearly neutral oxidative conditions

Beilstein Journal of Organic Chemistry ◽

10.3762/bjoc.14.149 ◽

2018 ◽

Vol 14 ◽

pp. 1750-1757 ◽

Cited By ~ 4

Author(s):

Shahien Shahsavari ◽

Chase McNamara ◽

Mark Sylvester ◽

Emily Bromley ◽

Savannah Joslin ◽

...

Keyword(s):

Aliphatic Amines ◽

Protecting Groups ◽

Protecting Group ◽

Weak Base ◽

Amino Groups ◽

Mild Conditions

The 1,3-dithiane-based dM-Dmoc group was studied for the protection of amino groups. Protection was achieved under mild conditions for aliphatic amines, and under highly reactive conditions for the less reactive arylamines. Moderate to excellent yields were obtained. Deprotection was performed by oxidation followed by treating with a weak base. The yields were good to excellent. The new amino protecting group offers a different dimension of orthogonality in reference to the commonly used amino protecting groups in terms of deprotection conditions. It is expected to allow a collection of transformations to be carried out on the protected substrates that are unattainable using any known protecting groups.

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The Preparation of pH- and Thermo-Sensitive Chitosan-Based Hydrogels by Michael-Type Addition Reaction

Applied Mechanics and Materials ◽

10.4028/www.scientific.net/amm.130-134.2392 ◽

2011 ◽

Vol 130-134 ◽

pp. 2392-2395

Author(s):

Hong Liang Wei ◽

Cun Cai Ma ◽

Hui Juan Chu ◽

Jing Zhu

Keyword(s):

Ethylene Glycol ◽

Potential Application ◽

Addition Reaction ◽

Poly Ethylene Glycol ◽

Amino Groups ◽

Mild Conditions ◽

Primary Amino ◽

Michael Type Addition ◽

Poly Ethylene ◽

Maleimide Group

The hydrogels based on chitosan were prepared by Michael-type addition reaction between chitosan's primary amino groups and maleimide group terminating poly (ethylene glycol) (PEG) under mild conditions. The hydrogels were characterizatied by FTIR, TG, etc. The study on the swelling behavior indicated that the hydrogels possess pH-and thermo-sensitivity. The chitosan-based hydogels crosslinked by Michael-type addition reaction have a potential application on biomaterials due to its biodegradability, biocompatibility, less toxicity and hydrophilicity.

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