6066-82-6Relevant articles and documents
TRPA1 is activated by direct addition of cysteine residues to the N-hydroxysuccinyl esters of acrylic and cinnamic acids
Sadofsky, Laura R.,Boa, Andrew N.,Maher, Sarah A.,Birrell, Mark A.,Belvisi, Maria G.,Morice, Alyn H.
, p. 30 - 36 (2011)
The nociceptor TRPA1 is thought to be activated through covalent modification of specific cysteine residues on the N terminal of the channel. The precise mechanism of covalent modification with unsaturated carbonyl-containing compounds is unclear, therefore by examining a range of compounds which can undergo both conjugate and/or direct addition reactions we sought to further elucidate the mechanism(s) whereby TRPA1 can be activated by covalent modification. Calcium signalling was used to determine the mechanism of activation of TRPA1 expressed in HEK293 cells with a series of related compounds which were capable of either direct and/or conjugate addition processes. These results were confirmed using physiological recordings with isolated vagus nerve preparations. We found negligible channel activation with chemicals which could only react with cysteine residues via conjugate addition such as acrylamide, acrylic acid, and cinnamic acid. Compounds able to react via either conjugate or direct addition, such as acrolein, methyl vinyl ketone, mesityl oxide, acrylic acid NHS ester, cinnamaldehyde and cinnamic acid NHS ester, activated TRPA1 in a concentration dependent manner as did compounds only capable of direct addition, namely propionic acid NHS ester and hydrocinnamic acid NHS ester. These compounds failed to activate TRPV1 expressed in HEK293 cells or mock transfected HEK293 cells. For molecules capable of direct or conjugate additions, the results suggest for the first time that TRPA1 may be activated preferentially by direct addition of the thiol group of TRPA1 cysteines to the agonist carbonyl carbon of α,β-unsaturated carbonyl-containing compounds.
DLL3-TARGETING MULTISPECIFIC ANTIGEN-BINDING MOLECULES AND USES THEREOF
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, (2021/10/02)
The disclosure provides multispecific antigen-binding molecules that comprise a first antigen-binding moiety and a second antigen-binding moiety, each of which is capable of binding to CD3 and CD137, but does not bind to CD3 and CD137 at the same time; and a third antigen-binding moiety that is capable of binding to DLL3, preferably human DLL3, which induce T-cell dependent cytotoxity more efficiently whilst circumventing adverse toxicity concerns or side effects that other multispecific antigen-binding molecules may have. The present invention provides multispecific antigen-binding molecules and pharmaceutical compositions that can treat various cancers, especially those associated with DLL3, by comprising the antigen-binding molecule as an active ingredient.
Synthesis method of N-(benzyloxycarbonyloxy)succinimide
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Paragraph 0005; 0008; 0012; 0015, (2020/05/05)
The invention relates to a synthesis method of N-(benzyloxycarbonyloxy)succinimide; the invention mainly solves the technical problems of high raw material cost, overhigh reaction rate, severe heat release, high possibility of generating impurities, high product loss during refining and the like in an existing synthesis method. The synthesis method comprises the following steps: dissociating hydroxylamine hydrochloride in an aqueous solution by using NaOH, and carrying out a reaction with succinic anhydride to generate HOSu; carrying out a reaction of HOSu with Cbz-Cl in a mixed solution of water and ethyl acetate to generate a target compound Cbz-OSu. Cbz-OSu is commonly used as a polypeptide commonly used reagent, and a Z-amino protection reagent is selectively introduced in synthesis ofamino acids and aminoglycoside antibiotics.
