Nature Communications May 13: Chiral Engineering of Tripeptide-Drug Conjugates Controls Liquid-Liquid Phase Separation vs β-Sheet Hydrogel Formation
A Nature Communications paper published May 13, 2026 reported that chiral engineering of tripeptide-drug conjugates (PDCs) — systematically varying the L/D amino-acid configuration in the peptide moiety — controls phase behavior between liquid-liquid phase separation (LLPS) and β-sheet-rich hydrogel formation. PDCs with alternating L/D residues underwent LLPS in solution; all-L or all-D PDCs formed structured hydrogels. The chirality-controlled phase behavior is a design lever for PDC drug-product engineering: LLPS-prone conjugates dissolve readily for parenteral dosing, while hydrogel-forming variants enable sustained-release depots or injection-site retention. The work expands the design space for peptide-drug conjugate formulation, joining the broader May 2026 PDC research cycle alongside the Avacta AVA6103 FOCUS-01 trial start and the Bicycle Therapeutics ASCO Duravelo-2 readout.