Design, Synthesis, and Biological Evaluation of Desmuramyl Dipeptides Modified by Adamantyl-1,2,3-triazole.

Muramyl dipeptide (MDP) is the smallest peptidoglycan fragment able to trigger the immune response. Structural modification of MDP can lead to the preparation of analogs with improved immunostimulant properties, including desmuramyl peptides (DMPs). The aim of this work was to prepare the desmuramyl peptide (L-Ala-D-Glu)-containing adamantyl-triazole moiety and its mannosylated derivative in order to study their immunomodulatory activities in vivo.

Dysregulated G2 phase checkpoint recovery pathway reduces DNA repair efficiency and increases chromosomal instability in a wide range of tumours.

Defective DNA repair is being demonstrated to be a useful target in cancer treatment. Currently, defective repair is identified by specific gene mutations, however defective repair is a common feature of cancers without these mutations. DNA damage triggers cell cycle checkpoints that are responsible for co-ordinating cell cycle arrest and DNA repair.

Bioevaluation of glucose-modified liposomes as a potential drug delivery system for cancer treatment using 177-Lu radiotracking.

Liposomes are promising drug's delivery systems due to decreased toxicity of the liposome-encapsulated drug, but wider clinical application requires their more efficient tumor targeting with uptake, controlled drug release and higher shelf life. The unique metabolic characteristics of cancer cells based on higher demand for energy and therefore increased glucose utilization were exploited in the design of glucose modified liposomes (GML) with the aim to provide increased tumor targeting via glucose transporters and increased ability of drug delivery into tumor cells. Tumor accumulating potential of GML and non-glucose liposomes (NGL) were investigated on CT26 and LS174T tumor-bearing mice by simple and reliable radiotracer method using Lu as radioactive marker.

Impact of C28 Oligosaccharide on Adjuvant Activity of QS-7 Analogues.

We have synthesized a number of Molina (QS) saponin analogues with a different C28 sugar unit, which features either 3,4-diacetyl groups or a 3,4-cyclic carbonate group at the reducing end fucoside to mimic the naturally occurring saponin adjuvant QS-7. Immunological evaluations of these analogues in BALB/c mice indicate that truncating the C28 oligosaccharide of the natural product to the tetrasaccharide (as in (β)) could retain the adjuvant's activity in enhancing IgG1 and IgG2a productions, albeit the activity is lower than that of QS-21. Further truncation or changing stereochemistry of glycosidic linkage between the tetrasaccharide and the triterpenoid quillaic acid (QA) core or within the tetrasaccharide eliminated the saponins' adjuvant activity in terms of IgG production.

Melanoma mutations modify melanocyte dynamics in co-culture with keratinocytes or fibroblasts.

Melanocytic cell interactions are integral to skin homeostasis, and affect the outcome of multiple diseases, including cutaneous pigmentation disorders and melanoma. By using automated-microscopy and machine-learning-assisted morphology analysis of primary human melanocytes in co-culture, we performed combinatorial interrogation of melanocyte genotypic variants and functional assessment of lentivirus-introduced mutations. Keratinocyte-induced melanocyte dendricity, an indicator of melanocyte differentiation, was reduced in the melanocortin 1 receptor (MC1R) R/R variant strain and by NRAS.