Rational design of peptides for identification of linear epitopes and generation of neutralizing monoclonal antibodies against DKK2 for cancer therapy.
Dickkopf-related protein 2 (DKK2)is a member of the Dickkopf household in Wnt signaling pathway. Recently, we discovered that antibodies against DKK2 might activate pure killer (NK) and CD8+ T cells in tumors and inhibit tumor development. In this paper, we report the rational design of peptides for identification of linear epitopes and generation of neutralizing monoclonal anti-DKK2 antibodies.
To break the immune tolerance, we designed and chemically synthesized six peptides akin to completely different areas of DKK2 as immunogens and discovered 5 of them might generate mouse polyclonal antibodies that may bind to the lively recombinant human DKK2 protein.
Description: Nicotinamide is a form of vitamin B3 or niacin. Nicotinamide Hydrochloride inhibits SIRT2 activity (IC50: 2 μM). Nicotinamide also inhibits SIRT1. Nicotinamide increases cellular NAD+, ATP, ROS levels. Nicotinamide inhibits tumor growth and improves survival. Nicotinamide also has anti-HBV activity[1][2][3][4].
Description: IC50: N/ANicotinamide is an inhibitor of poly(ADP-ribose) polymerase (PARP-1) enzymes. Poly(ADP-ribose) polymerase-1 (PARP-1) is found as a DNA repair enzyme.
Description: Nicotinamide-13C6 is the 13C-labeled Nicotinamide. Nicotinamide is a form of vitamin B3 that plays essential roles in cell physiology through facilitating NAD+ redox homeostasis and providing NAD+ as a substrate to a class of enzymes that catalyze non-redox reactions. Nicotinamide is an inhibitor of SIRT1.
Description: Nicotinamide-d4 is the deuterium labeled Nicotinamide. Nicotinamide is a form of vitamin B3 that plays essential roles in cell physiology through facilitating NAD+ redox homeostasis and providing NAD+ as a substrate to a class of enzymes that catalyze non-redox reactions. Nicotinamide is an inhibitor of SIRT1.
Description: Nicotinamide-15N,13C3 is the 13C-labeled and 15N-labeled Nicotinamide. Nicotinamide is a form of vitamin B3 that plays essential roles in cell physiology through facilitating NAD+ redox homeostasis and providing NAD+ as a substrate to a class of enzymes that catalyze non-redox reactions. Nicotinamide is an inhibitor of SIRT1.
Description: Nicotinamide (Standard) is the analytical standard of Nicotinamide. This product is intended for research and analytical applications. Nicotinamide is a form of vitamin B3 or niacin. Nicotinamide Hydrochloride inhibits SIRT2 activity (IC50: 2 μM). Nicotinamide also inhibits SIRT1. Nicotinamide increases cellular NAD+, ATP, ROS levels. Nicotinamide inhibits tumor growth and improves survival. Nicotinamide also has anti-HBV activity[1][2][3][4].
Description: Nicotinamide riboside, an orally active NAD+ precursor, increases NAD+ levels and activates SIRT1 and SIRT3. Nicotinamide riboside is a source of vitamin B3 (niacin) and enhances oxidative metabolism, protection against high fat diet-induced metabolic abnormalities[1]. Nicotinamide riboside reduces cognitive deterioration in a transgenic mouse model of Alzheimer’s disease[2].
Description: Nicotinamide riboside malate, an orally active NAD+ precursor, increases NAD+ levels and activates SIRT1 and SIRT3. Nicotinamide riboside malate is a source of vitamin B3 (niacin) and enhances oxidative metabolism, protection against high fat diet-induced metabolic abnormalities[1]. Nicotinamide riboside malate reduces cognitive deterioration in a transgenic mouse model of Alzheimer’s disease[2].
Description: Nicotinamide riboside Chloride, an orally active NAD+ precursor, increases NAD+ levels and activates SIRT1 and SIRT3. Nicotinamide riboside Chloride is a source of vitamin B3 (niacin) and enhances oxidative metabolism, protection against high fat diet-induced metabolic abnormalities[1]. Nicotinamide riboside Chloride reduces cognitive deterioration in a transgenic mouse model of Alzheimer’s disease[2].
Description: Nicotinamide riboside tartrate, an orally active NAD+ precursor, increases NAD+ levels and activates SIRT1 and SIRT3. Nicotinamide riboside tartrate is a source of vitamin B3 (niacin) and enhances oxidative metabolism, protection against high fat diet-induced metabolic abnormalities[1]. Nicotinamide riboside tartrate reduces cognitive deterioration in a transgenic mouse model of Alzheimer’s disease[2].
Neutralizing mousemonoclonalantibodies (5F8 and 1A10) against human DKK2 have been efficiently developed by immunizing the mice with two completely different peptides (34KLNSIKSSL42 and 240KVWKDATYS248) conjugated to Keyhole limpet hemocyanin (KLH). The monoclonalantibodies not solely abolish DKK2’s suppression of Wnt signaling in vitro but additionally inhibits tumor development in vivo. Currently, these two mAbs are present process humanization as immunotherapy candidates and could provide a brand new drug for remedy of human cancers.