H-D-Arg-OH is a D-configuration non-natural amino acid with important applications in drug development and protein engineering[1-2]. H-D-Arg-OH is commonly used in studies related to the L-arginine/nitric oxide pathway and has shown potential in inhibiting the proliferation of certain cancer cells[3-4].
In vitro, pretreatment of pituitary GH3 cells with H-D-Arg-OH (10mM) for 15–240 minutes, followed by incubation in normal Krebs solution, significantly increased intracellular D-arginine concentration and nitric oxide (NO) production, while also elevating extracellular nitrite levels[5]. Combined pretreatment of Actinomyces viscosus biofilms with 8mM H-D-Arg-OH and 0.01% α-amylase (Amy) for 30 minutes significantly enhanced the dissociation effect of α-amylase on the biofilm, completely hydrolyzing extracellular polysaccharides while maintaining safety toward MC3T3-E1 pre-osteoblasts[6].
In vivo, oral administration of H-D-Arg-OH (1000mg/kg/day) via drinking water to 9-week-old male Sprague-Dawley rats for 16 weeks significantly increased endothelial nitric oxide synthase (eNOS) protein expression in the kidneys and aorta, while also raising urea levels in skeletal muscle[7]. After oral administration of H-D-Arg-OH (6mmol/10mL DW/kg) to ICR mice for 30, 60, and 90 minutes, a significant increase in H-D-Arg-OH levels was observed in both plasma and brain tissues[8].
References:
[1] Navarro E, Alonso SJ, Martín FA, et al. Toxicological and pharmacological effects of D-arginine. Basic Clin Pharmacol Toxicol. 2005 Sep;97(3):149-54.
[2] Kawabata A, Nishimura Y, Takagi H. L-leucyl-L-arginine, naltrindole and D-arginine block antinociception elicited by L-arginine in mice with carrageenin-induced hyperalgesia. Br J Pharmacol. 1992 Dec;107(4):1096-101.
[3] Hu B, Feng X, Wang L, et al. 5-BDBD ameliorates an OVA-induced allergic asthma by the reduction of Th2 cytokines production. Iran J Basic Med Sci. 2018 Apr;21(4):364-369.
[4] Wang L, Wu J, Wang B, et al. d-arginine-functionalized carbon dots with enhanced near-infrared emission and prolonged metabolism time for tumor fluorescent-guided photothermal therapy. J Colloid Interface Sci. 2025 Jan 15;678(Pt C):575-582.
[5] Melisi D, Secondo A, Montoro P, et al. Galactosyl derivatives of L-arginine and D-arginine: synthesis, stability, cell permeation, and nitric oxide production in pituitary GH3 cells. J Med Chem. 2006 Aug 10;49(16):4826-33.
[6] Li B, Cai Q, Wang Z, et al. D-arginine Enhances the Effect of Alpha-Amylase on Disassembling Actinomyces viscosus Biofilm. Front Bioeng Biotechnol. 2022 Mar 3;10:864012.
[7] Kim DR, Martin S, Desai K. The effects of a comparatively higher dose of 1000 mg/kg/d of oral L- or D-arginine on the L-arginine metabolic pathways in male Sprague-Dawley rats. PLoS One. 2023 Aug 1;18(8):e0289476.
[8] Aso K, Nishigawa T, Nagamachi S, et al. Orally administrated D-arginine exhibits higher enrichment in the brain and milk than L-arginine in ICR mice. J Vet Med Sci. 2020 Mar 5;82(3):307-313.