Abstract 1304: AbYlinkTM: A site-selective labeling method for preclinical imaging of therapeutic antibodies

2021 ◽  
Author(s):  
Viktoriia Postupalenko ◽  
Léo Marx ◽  
David Viertl ◽  
Natalia Gasilova ◽  
Mathilde Plantin ◽  
...  
Keyword(s):  
Therapeutic Antibodies ◽  
Selective Labeling ◽  
Preclinical Imaging ◽  
A Site ◽  
Site Selective ◽  
Labeling Method

scholarly journals Protein Conjugation with Triazolinediones: Switching from a General Tyrosine-Selective Labeling Method to a Highly Specific Tryptophan Bioconjugation Strategy

2021 ◽  
Author(s):  
Klaas Decoene ◽  
Kamil Unal ◽  
An Staes ◽  
Kris Gevaert ◽  
Johan M. Winne ◽  
...  
Keyword(s):  
Unnatural Amino Acids ◽  
Click Reaction ◽  
Selective Labeling ◽  
Site Specific ◽  
Tyrosine Residues ◽  
Tryptophan Residues ◽  
Low Levels ◽  
Almost All ◽  
Site Selective ◽  
Labeling Method

Selective labeling of tyrosine residues in peptides and proteins can be achieved via a 'tyrosine-click' reaction with triazolinedione reagents (TAD). We have found that tryptophan residues are in fact often also labeled with this reagent. This off-target labeling is only observed at very low levels in protein bioconjugation but remains under the radar due to the low relative abundance of tryptophan compared to tyrosines in natural proteins, and because of the low availability and accessibility of their nucleophilic positions at the solvent-exposed protein surface. Moreover, because TAD-Trp adducts are known to be readily thermoreversible, it can be challenging to detect these physiologically stable but thermally labile modifications using several MS/MS techniques. We have found that fully solvent-exposed tryptophan side chains are kinetically favored over tyrosines under almost all conditions, and this selectivity can even be further enhanced by modifying the pH of the aqueous buffer to effect selective Trp-labeling. This new site-selective bioconjugation method does not rely on unnatural amino acids and has been demonstrated for peptides and for recombinant proteins. Thus, the TAD-Tyr click reaction can be turned into a highly site-specific labeling method for tryptophan.

scholarly journals Protein Conjugation with Triazolinediones: Switching from a General Tyrosine-Selective Labeling Method to a Highly Specific Tryptophan Bioconjugation Strategy

2021 ◽  
Author(s):  
Klaas Decoene ◽  
Kamil Unal ◽  
An Staes ◽  
Kris Gevaert ◽  
Johan M. Winne ◽  
...  
Keyword(s):  
Unnatural Amino Acids ◽  
Click Reaction ◽  
Selective Labeling ◽  
Site Specific ◽  
Tyrosine Residues ◽  
Tryptophan Residues ◽  
Low Levels ◽  
Almost All ◽  
Site Selective ◽  
Labeling Method

Selective labeling of tyrosine residues in peptides and proteins can be achieved via a 'tyrosine-click' reaction with triazolinedione reagents (TAD). We have found that tryptophan residues are in fact often also labeled with this reagent. This off-target labeling is only observed at very low levels in protein bioconjugation but remains under the radar due to the low relative abundance of tryptophan compared to tyrosines in natural proteins, and because of the low availability and accessibility of their nucleophilic positions at the solvent-exposed protein surface. Moreover, because TAD-Trp adducts are known to be readily thermoreversible, it can be challenging to detect these physiologically stable but thermally labile modifications using several MS/MS techniques. We have found that fully solvent-exposed tryptophan side chains are kinetically favored over tyrosines under almost all conditions, and this selectivity can even be further enhanced by modifying the pH of the aqueous buffer to effect selective Trp-labeling. This new site-selective bioconjugation method does not rely on unnatural amino acids and has been demonstrated for peptides and for recombinant proteins. Thus, the TAD-Tyr click reaction can be turned into a highly site-specific labeling method for tryptophan.

Chemical and Electrochemical Heteroepitaxial Growth of Chalcogenide Semiconductors from Solutions

1996 ◽  
Vol 451 ◽  
Author(s):  
D. Lincot ◽  
M. J. Furlong ◽  
M. Froment ◽  
R. Cortes ◽  
M. C. Bernard
Keyword(s):  
Heteroepitaxial Growth ◽  
X Ray Diffraction ◽  
Basic Principles ◽  
Lattice Match ◽  
X Ray ◽  
Chalcogenide Semiconductors ◽  
Influence Of Temperature On ◽  
Deposition Processes ◽  
A Site ◽  
Site Selective

ABSTRACTChalcogenide semiconductors have been deposited epitaxially from aqueous solutions either chemically or electrochemically at growth rates of up to 0.7 μmhr−1. After recalling the basic principles of these deposition processes, results are presented concerning chemically deposited CdS on InP, GaP and CuInSe2 substrates, electrodeposited CdTe on InP, and CdSAnP heterostructures. Characterisation of these structures by RHEED, TEM, HRTEM, and glazing angle X ray diffraction allows to analyse the effects of substrate orientation, polarity, lattice match plus the influence of temperature on epitaxial growth. These results are discussed in terms of self organisation and a site selective growth mechanisms due to the free enegy of formation of each compound.

A Site‐Selective C−N Bond Formation of 2,4‐Dichloro‐5 H ‐pyrano[2,3‐ d ]pyrimidines and Amide

2021 ◽  
Vol 6 (43) ◽  
pp. 12032-12035
Author(s):  
Jinjing Qin ◽  
Zhenhua Li ◽  
Yingyan Cao ◽  
Yuanyuan Xie ◽  
Weike Su
Keyword(s):  
Bond Formation ◽  
A Site ◽  
Site Selective

Catalyst-Controlled Site-Selective N-H and C3-Arylation of Carba-zole via Carbene Transfer Reactions

2021 ◽  
Author(s):  
Sourav Sekhar Bera ◽  
Srishti Ballabh Bahukhandi ◽  
Claire Empel ◽  
Rene M Koenigs
Keyword(s):  
Transfer Reactions ◽  
Palladium Acetate ◽  
Direct Arylation ◽  
Carbene Transfer ◽  
A Site ◽  
Site Selective

A site-selective direct arylation reaction of carbazole and other N-heterocycles with diazo-naphthalen-2(1H)-ones has been developed. While Au(I)-NHC catalysts lead to selective C3-arylation, palladium acetate allows for selective N-H arylation, displaying...

Nickel-Catalyzed Regioselective Carbomagnesation of Methylenecyclopropanes through a Site-Selective Carbon-Carbon Bond Cleavage

2009 ◽  
Vol 49 (1) ◽  
pp. 144-147 ◽  
Author(s):  
Jun Terao ◽  
Masahiro Tomita ◽  
Surya Prakash Singh ◽  
Nobuaki Kambe
Keyword(s):  
Bond Cleavage ◽  
Carbon Bond ◽  
Carbon Carbon Bond ◽  
A Site ◽  
Site Selective

scholarly journals Bioinspired Thiophosphorodichloridate Reagents for Chemoselective Histidine Bioconjugation

2018 ◽  
Author(s):  
Shang Jia ◽  
Christopher Chang
Keyword(s):  
Protein Function ◽  
Living Cells ◽  
Covalent Modification ◽  
Native Protein ◽  
Selective Labeling ◽  
Protein Residues ◽  
Mild Conditions ◽  
Starting Point ◽  
Histidine Phosphorylation ◽  
Site Selective

Site-selective bioconjugation to native protein residues is a powerful tool for protein functionalization, with cysteine and lysine side chains being the most common points for attachment owing to their high nucleophilicity. We now report a strategy for histidine modification using thiophosphorodichloridate reagents that mimic post-translational histidine phosphorylation, enabling fast and selective labeling of protein histidines under mild conditions where various payloads can be introduced via copper-assisted alkyne-azide cycloaddition (CuAAC) chemistry. We establish that these reagents are particularly effective at covalent modification of His-tags, which are common motifs to facilitate protein purification, as illustrated by selective attachment of polyarginine cargoes to enhance the uptake of proteins into living cells. This work provides a starting point for probing and enhancing protein function using histidine-directed chemistry.

scholarly journals Site-Selective C-C Modification of Proteins at Neutral pH Using Organocatalyst-Mediated Cross Aldol Ligations

2018 ◽  
Author(s):  
Martin A. Fascione ◽  
Richard J. Spears ◽  
Robin L. Brabham ◽  
Darshita Budhadev ◽  
Tessa Keenan ◽  
...  
Keyword(s):  
Small Molecules ◽  
Stable Carbon ◽  
Biological Mechanisms ◽  
Large Excess ◽  
Reaction Conditions ◽  
Chemical Methods ◽  
Neutral Ph ◽  
Chemical Modification Of Proteins ◽  
A Site ◽  
Site Selective

The bioconjugation of proteins with small molecules has proved an invaluable strategy for probing and perturbing dynamic biological mechanisms. The general use of chemical methods for the functionalisation of proteins remains limited however by the frequent requirement for complicated reaction partners to be present in large excess, and harsh reaction conditions which are incompatible with many protein scaffolds. Herein we describe a site-selective organocatalyst-mediated protein aldol ligation (OPAL) that affords stable carbon-carbon linked bioconjugates at neutral pH under biocompatible conditions. OPAL enables rapid chemical modification of proteins within an hour using simple aldehyde probes in minimal excess, and is utilised here in the selective affinity tagging of proteins in cell lysate. Furthermore we demonstrate that the b-hydroxy aldehyde product of the OPAL can be functionalised a second time at neutral pH in a subsequent organocatalyst-mediated oxime ligation. This tandem strategy is showcased in the ‘chemical mimicry’ of a previously inaccessible natural dual post-translationally modified protein integral to the pathogenesis of the neglected tropical disease Leishmaniasis. <br>

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