The effect of autophagy-enhancing peptide in moisturizer on atopic dermatitis: a randomized controlled trial.

Pentasodium tetracarboxymethyl palmitoyl dipeptide-12 (PTPD-12), a newly-synthesized peptide, enhances the autophagy activity, ultimately managing inflammation. To determine the effect of a new moisturizer containing PTPD-12 as the treatment of mild-to-moderate atopic dermatitis (AD). In this double-blind, randomized, placebo-controlled trial, 43 patients with mild-to-moderate AD were randomly assigned to either the PTPD-12 or control groups.

1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol ameliorates arthritic joints through reducing neutrophil infiltration mediated by IL-6/STAT3 and MIP-2 activation.

The pathogenesis of rheumatoid arthritis (RA) has been implicated neutrophil extracellular traps (NETs) formation which could generate autoantigen. Neutrophil contributes to initiate and maintain the inflammatory process in the joint. In this study, we show that 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) decreases neutrophil migration by regulating the activity of STAT3, a regulator of IL-6 and MIP-2 expression.

Unique binding mode of Evogliptin with human dipeptidyl peptidase IV.

Evogliptin ((R)-4-((R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl)-3-(tert-butoxymethyl) piperazine-2-one)) is a highly potent selective inhibitor of dipeptidyl peptidase IV (DPP4) that was approved for the treatment of type 2 diabetes in South Korea. In this study, we report the crystal structures of Evogliptin, DA-12166, and DA-12228 (S,R diastereomer of Evogliptin) complexed to human DPP4. Analysis of both the structures and inhibitory activities suggests that the binding of the trifluorophenyl moiety in the S pocket and the piperazine-2-one moiety have hydrophobic interactions with Phe357 in the S extensive subsite, and that the multiple hydrogen bonds made by the (R)-β-amine group in the S pocket and the contacts made by the (R)-tert-butyl group with Arg125 contribute to the high potency observed for Evogliptin.

The Therapeutic Effect of PLAG against Oral Mucositis in Hamster and Mouse Model.

Chemotherapy-induced mucositis can limit the effectiveness of cancer therapy and increase the risk of infections. However, no specific therapy for protection against mucositis is currently available. In this study, we investigated the therapeutic effect of PLAG (1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol, acetylated diglyceride) in 5-fluorouracil (5-FU)-induced oral mucositis animal models.

Negatively-charged amino acids at the peptide-binding pocket of HLA-DPB1 alleles are associated with susceptibility to anti-topoisomerase I-positive systemic sclerosis.

We investigated shared characteristics of amino acid sequences in the at risk HLA-DPB1 alleles in systemic sclerosis (SSc). Amino acid sequences and their structural features of HLA-DP molecules in 127 Korean SSc patients and 548 healthy Korean controls were analyzed with a focus on known HLA-DP binding motifs. The binding grooves containing more negatively-charged triplets (NCT) had higher odds ratios of anti-topoisomerase I antibody (ATA)-positive SSc.

PLAG (1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol) augments the therapeutic effect of pegfilgrastim on gemcitabine-induced neutropenia.

Granulocyte colony-stimulating factor (G-CSF) is widely used for preventing neutropenia during chemotherapy. Polyethylene glycol-conjugated granulocyte colony-stimulating factor (PEG-G-CSF, pegfilgrastim) serves the same purpose but has a longer half-life and greater stability than G-CSF. In this study, we investigated whether 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol, acetylated diglyceride (PLAG), augments the therapeutic effect of pegfilgrastim on chemotherapy-induced neutropenia.

PLAG (1-Palmitoyl-2-Linoleoyl-3-Acetyl-rac-Glycerol) Modulates Eosinophil Chemotaxis by Regulating CCL26 Expression from Epithelial Cells.

Increased number of eosinophils in the circulation and sputum is associated with the severity of asthma. The respiratory epithelium produces chemokine (C-C motif) ligands (CCL) which recruits and activates eosinophils. A chemically synthesized monoacetyl-diglyceride, PLAG (1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol) is a major constituent in the antlers of Sika deer (Cervus nippon Temminck) which has been used in oriental medicine.

Protective effect of EC-18, a synthetic monoacetyldiglyceride on lung inflammation in a murine model induced by cigarette smoke and lipopolysaccharide.

The antler of Sika deer (Cervus nippon Temminck) has been used a natural medicine in Korea, China and Japan, and a monoacetyldiaglyceride (1-palmitoyl-2-linoleoyl-3-acetylglycerol, PLAG) was found in the antler of Sika deer as a constituent for immunomodulation. In this study, we investigated protective effects of EC-18 (a synthetic copy of PLAG) on inflammatory responses using a cigarette smoke with lipopolysaccharide (LPS)-induced airway inflammation model. Mice were exposed to cigarette smoke for 1h per day for 3days.

Dipeptidyl peptidase-4 inhibitor with β-amino amide scaffold: synthesis, SAR and biological evaluation.

Inhibitors of dipeptidyl peptidase-4 (DPP4) have been shown to be effective treatments for type 2 diabetes. Several series of β-amino amide containing piperazine derivatives have been prepared and evaluated as a inhibitor of DPP4. Finally compound 5m was selected for further evaluation.

DA-1229, a novel and potent DPP4 inhibitor, improves insulin resistance and delays the onset of diabetes.

Aim: To characterize the pharmacodynamic profile of DA-1229, a novel dipeptidyl peptidase (DPP) 4 inhibitor.

Main Methods: Enzyme inhibition assays against DPP4, DPP8 and DPP9. Antidiabetic effects of DA-1229 in HF-DIO mice and young db/db mice.

Discovery of DA-1229: a potent, long acting dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes.

A series of β-amino amide containing substituted piperazine-2-one derivatives was synthesized and evaluated as inhibitors of dipeptidyl pepdidase-4 (DPP-4) for the treatment of type 2 diabetes. As results of intensive SAR study of the series, (R)-4-[(R)-3-amino-4-(2,4,5-trifluorophenyl)-butanoyl]-3-(t-butoxymethyl)-piperazin-2-one (DA-1229) displayed potent DPP-4 inhibition pattern in several animal models, was selected for clinical development.

A novel dipeptidyl peptidase IV inhibitor DA-1229 ameliorates streptozotocin-induced diabetes by increasing β-cell replication and neogenesis.

We studied the effect of a novel dipeptidyl peptidase IV (DPP IV) inhibitor, DA-1229, on blood glucose profile and pancreatic β-cell mass in established diabetes after streptozotocin (STZ) treatment. Mice that developed diabetes after administration of STZ 100mg/kg were treated with DA-1229 for 13 weeks. DA-1229 significantly reduced plasma DPP IV activity, and enhanced glucagon-like peptide 1 (GLP-1) levels.

A novel L-ascorbic acid and peptide conjugate with increased stability and collagen biosynthesis.

L-ascorbic acid (Vitamin C) and peptide are both useful compounds for collagen biosynthesis in cosmeceuticals (cosmetic and pharmaceutical fields). The instability of these compounds, however, limit their application in these industries. In this report, we describe the development of a novel compound, Stabilized Ascorbyl Pentapeptide (SAP), which physically is much more stable than L-ascorbic acid in water.

Design and efficient synthesis of novel ascorbyl conjugated peptide with high collagen biosynthesis stimulating effects.

Collagen is critical for skin strength and elasticity, and its degradation leads to wrinkles that accompany aging. Based emphasis on the aesthetics, we tried to make a new compound that can highly stimulate collagen biosynthesis and synthesized ascorbyl conjugated peptide that is a complex form connected by succinoyl linker. We conducted several in vitro and in vivo experiments to identify if the compound has a potent activity, comparing to the ascorbic acid only for collagen biosynthesis.