Hydrophilic poly(ethylene glycol) or PEG-linkers are particularly attractive as a linker for conjugation. Water solubility, lack of toxicity; low immunogenicity and well defined chain lengths and molecular weights are specific characteristics of PEG moieties relevant to pharmaceutical applications.
The link between the antibody and the cytotoxic agent plays a critical role in development of antibody-drug conjugates. The nature of the linker can significantly affect the potency, selectivity, and the pharmacokinetics of an antibody-drug conjugate.
A common feature of numerous linkers used to prepare antibody-drug conjugates is their hydrophobicity – or their inability to dissolve in water. In most cases, the average drug-to-antibody ratio (DAR) or the number of drug molecules per antibody does not exceed 3-4 drug molecules per antibody molecule.
Many of the problems seen with hydrophobic linkers can be overcome by sulfonate- or PEG-containing hydrophilic linkers which are characterized by high solubility in both organic and aqueous solutions.
Furthermore, branched or multi-arm PEG linkers enable conjugation of hydrophobic organic molecule drugs, such as a maytansinoid, at a higher rations of DAR than hydrophobic SPDB and SMCC linkers used earlier without triggering aggregation or loss of affinity of the resulting conjugate. This, in turn, results in the ability to deliver a higher concentration of cytotoxic drug into the target cells per antibody binding event.
This “doubled payload” approach can enhance the potency of an antibody-drug conjugate with hydrophilic linkers disproportionately 10 to 100-fold in vivo. One study showed that the use of PEG-linkers resulted in a dramatically improved pharmacokinetic profiles in vivo, with a prolonged half-life, increased plasma concentration, and increased area under the plasma concentration-time curve (AUC). These effect can be especially advantageous if the target antigen density is low.
Biochempeg has over 3000 high purity PEG linkers in stock to empower your PEGylation, bioconjugation, crosslinking, ADC drug development, biolabeling for pharmaceutical and biotech R&D, such as mPEG, Biotin PEG, Silane PEG, Amine PEG, Azide PEG, Acrylamide PEG, Maleimide PEG, DSPE PEG, NHS ester PEG, DBCO PEG, and others. It develops a broad range of PEG linkers and provides custom linker synthesis for clients worldwide.
CatalogID: 12262 Purity: ≥95% CAS NO.: 2182602-17-9
CatalogID: NA Purity: ≥95% CAS NO.: 2055042-56-1
CatalogID: NA Purity: ≥95% CAS NO.: 2055033-05-9
CatalogID: 12247 Purity: ≥95% CAS NO.: 1807518-72-4
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