PT  - JOURNAL ARTICLE
AU  - Sebastian Makuch
AU  - Marta Woźniak
AU  - Monika Krawczyk
AU  - Gabriela Pastuch-Gawołek
AU  - Wiesław Szeja
AU  - Siddarth Agrawal
TI  - Glycoconjugation as a promising treatment strategy for psoriasis
AID  - 10.1124/jpet.119.263657
DP  - 2020 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - jpet.119.263657
4099  - http://jpet.aspetjournals.org/content/early/2020/03/10/jpet.119.263657.short
4100  - http://jpet.aspetjournals.org/content/early/2020/03/10/jpet.119.263657.full
AB  - Despite the progress in the development of novel treatment modalities, a significant portion of patients with psoriasis remains undertreated relative to the severity of their disease. Recent evidence points to targeting the glucose transporter GLUT1 and sugar metabolism as a novel therapeutic strategy for the treatment of psoriasis and other hyperproliferative skin diseases. In this review, we discuss glycoconjugation, an approach that facilitates the pharmacokinetics of cytotoxic molecules and ensures their preferential influx through glucose transporters. We propose pathways of glycoconjugate synthesis to increase effectiveness, cellular selectivity, and tolerability of widely-used antipsoriatic drugs. The presented approach exploiting the heightened glucose requirement of proliferating keratinocytes bears the potential to revolutionize the management of psoriasis.SIGNIFICANCE STATEMENT Recent findings concerning the fundamental role of enhanced glucose metabolism and GLUT1 overexpression in the pathogenesis of psoriasis brought to light approaches that proved successful in cancer treatment. Substantial advances in the emerging field of glycoconjugation highlight the rationale for the development of glucose-conjugated antipsoriatic drugs to increase their effectiveness, cellular selectivity, and tolerability. The presented approach offers a novel therapeutic strategy for the treatment of psoriasis and other hyperproliferative skin diseases.