[D-Gln4]LR

**[D-Gln4]LR** is a synthetic linear octapeptide analog derived from the peptide LR, in which the fourth amino acid (glutamine) is present in the D-configuration instead of the natural L-configuration. The sequence is Leu-Ser-Cys-D-Gln-Leu-Tyr-Gln-Arg. [D-Gln4]LR is designed as an allosteric inhibitor of human thymidylate synthase (hTS), stabilizing its inactive conformation and inhibiting dTMP biosynthesis, a critical pathway for DNA synthesis in cancer cells. In vitro and cell studies demonstrate that [D-Gln4]LR, like its parent LR, inhibits cancer cell growth primarily by reducing the abundance of the active hTS conformation. The D-Gln substitution enhances peptide stability against enzymatic degradation. Variants and formulations, including conjugation to folic acid and encapsulation into liposomal delivery systems, are under investigation to improve selectivity and delivery for anticancer therapy[1][3][5].

Other names

Leu-Ser-Cys-D-Gln-Leu-Tyr-Gln-Arglinear [D-Gln4]LR