AEEA-AEEA

AEEA-AEEA CAS 1143516-05-5 is a typical PEG based diamino linker, whose molecular structure consists of two AEEA units connected end-to-end by amide bonds, with one free primary amino group retained at each end. The middle skeleton is rich in ethylene glycol repeating units (- O-CH ₂ - CH ₂ -) and amide bonds. This structure endows it with unique "flexible hydrophilic bifunctional" characteristics.
Firstly, PEG segments provide excellent hydrophilicity and conformational flexibility. Each ether oxygen atom can bind 2-3 water molecules to form a thick hydration layer, significantly reducing the hydrophobicity of the linker drug loading. Secondly, both ends of the amino group are primary amines with high reactivity, which can be directly coupled with carboxyl, activated ester or isocyanate groups without the need for additional activation. Furthermore, the molecular length is approximately 2.0-2.5 nm, which is suitable for maintaining an appropriate distance between antibodies and drugs to avoid steric hindrance affecting antigen binding affinity.
The synthetic advantage is manifested in the preparation of AEEA-AEEA mainly using liquid-phase or solid-phase condensation strategies. The simplest method is to directly couple two molecules of AEEA monomers in the presence of a condensing agent (HATU/DIC+Oxyma), with a yield of over 85%. The key advantage lies in: ① Both AEEA monomers are commercially available and come with Fmoc/Boc protection group options for orthogonal protection; ② The formation conditions of amide bonds are mild and do not require extreme pH or high temperature; ③ The purification of the product is easy, and high-purity (>98%) products can be obtained through reverse chromatography or recrystallization. In solid-phase peptide synthesis (SPPS), AEEA-AEEA can be directly loaded as a dipeptide module, with coupling efficiency usually>99%, and side reactions (such as the formation of diketopiperazine) are much lower than traditional dipeptides. These synthetic advantages make it one of the most popular PEG linkers in ADC, PROTAC, and peptide drug modification.