A preclinical team got a triple-modified probe peptide — Dmt, a disulfide bridge, an acetyl cap — to 5 g in nine weeks

Challenge

The team was building a research tool for a receptor-pharmacology question and the design called for three modifications in one molecule: a non-natural Dmt residue (the same family as the Dmt in SS-31), an intramolecular disulfide bridge tying positions 3 and 9, and an N-terminal acetyl cap. Sourcing had stalled — the quotes coming back from other SPPS houses ranged from "two of the three is fine" to an outright "we won't run Dmt together with disulfide cyclisation." What the Head of Chemistry actually needed was one supplier willing to carry the full modification stack on a research-programme clock.

Approach

Lyochem confirmed the whole stack sat inside the lab's routine SPPS scope and opened with a 200 mg pilot. The build used Fmoc-protected Dmt building blocks, a controlled oxidative fold tuned to favour the intramolecular disulfide over scrambled intermolecular isomers, and acetic-anhydride capping at the N-terminus. Release documentation leaned on the fact that each modification leaves its own signature: ESI-MS resolved all three at once — Dmt at +28 Da against native Tyr, the disulfide at -2 Da against the reduced linear form, and the acetyl at +42 Da against the free amine — backed by an LC-MS/MS read covering both arms across the bridge, alongside HPLC at ≥99.1 % measured purity.

Outcome

The pilot reached the buyer five weeks after the signed brief. A 5 g scale-up then ran concurrently with the team's pharmacology validation, landing at the nine-week mark. The route is now locked for reorders, and the programme has continued drawing against a quarterly forecast with no re-validation overhead on subsequent lots.