RE:RE:RE:RE:Whats this?I started to read the article, but just at the chemistry section I was baffled. First they finally give the amino acids sequence of TH19P01 which is:
Acetyl-Gly-Val-Arg-Ala-Lys-Ala-Gly-Val-Arg-Asn-(Nle)-Phe-Lys-Ser-Glu-Ser-Tyr
So they have two lysines (Lys) strategically situated on both side of the peptide, with a nice gap in the middle. It's on these two lysines that the linker + docetaxel will be achored to the peptide. They have an acetyl group on the N-terminus of the peptide to give it more stability against enzymatic cleavage, they also have a norleucine (Nle) in the middle, which is probably a more stable (non sulfur) replacement for methionine.
That being said what I don't understand in the chemistry part is the linker. They use succinic anhydride to attach docetaxel to the lysines on the peptide, leaving a linker structure that is not what I saw in one of their previous presentation where they were claiming to use dimethyl glutaryl linker. And in the article, after descrbing the chemical reactions they end up with a molecule called TH19P01(SuDoce)2 or TH1902. So they claim there that the PDC with the succinyl linker is TH1902. It does not make sense because the succinyl linker is not cleavable under physilogic conditions. It is categorized as a non cleavable linker for ADCs. So I really don't understand why they claim that TH1902 has a succinyl linker, while before, they claimed it was dimethyl glutaryl.
https://www.selleckchem.com/products/succinic-anhydride.html