When designing linker–payload systems for antibody–drug conjugates (ADCs), one of the most frequent requests we hear from partners is simple but challenging: deliver the payload as cleanly as possible.

In other words—no unwanted chemical residues, no “tails,” no structural scars on the active drug. This is exactly where traceless linkers make the difference.

What Makes Traceless Linkers Unique?

Traditional linkers often leave behind small chemical fragments on the drug after cleavage. While these remnants may seem minor, they can alter the payload’s properties—reducing potency, shifting pharmacokinetics, or introducing off-target effects.

Traceless linkers, on the other hand, are designed to fully disassemble upon trigger, releasing the unmodified, native payload. The result is a cleaner, more elegant pharmacological profile and a higher chance of maximizing therapeutic benefit.

How Do They Work?

Most traceless systems use self-immolative spacers—ingenious molecular architectures that undergo rapid fragmentation after a single trigger event. Once the cleavage point is activated (by enzymatic action, reduction, or pH change), the entire linker collapses, leaving behind only the intact drug.

Think of it as a molecular domino effect: ✂️ one cut, and the structure disappears.

Expertise at SigutLabs

At SigutLabs, we specialize in designing and synthesizing these smart linkers, tailored to the specific release strategy your payload requires. Our team has extensive experience with:

• Cathepsin-cleavable peptides

• Glucuronidase-cleavable motifs

• Reduction-sensitive disulfides

• pH-responsive designs

…and beyond. Each system can be tuned to achieve optimal release kinetics and stability for your program.

Let’s Collaborate

If you’re working on ADC development and need a partner experienced in traceless linker chemistry, we’d be delighted to support your project.

Contact us to discuss how SigutLabs can help accelerate your ADC program with customized linker–payload solutions.