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Last update 23 Jan 2025

DCPS

Last update 23 Jan 2025

Basic Info

Synonyms

5'-(N(7)-methyl 5'-triphosphoguanosine)-[mRNA] diphosphatase, DCPS, DCS-1

+ [12]

Introduction

Decapping scavenger enzyme that catalyzes the cleavage of a residual cap structure following the degradation of mRNAs by the 3'->5' exosome-mediated mRNA decay pathway. Hydrolyzes cap analog structures like 7-methylguanosine nucleoside triphosphate (m7GpppG) with up to 10 nucleotide substrates (small capped oligoribonucleotides) and specifically releases 5'-phosphorylated RNA fragments and 7-methylguanosine monophosphate (m7GMP). Cleaves cap analog structures like tri-methyl guanosine nucleoside triphosphate (m3(2,2,7)GpppG) with very poor efficiency. Does not hydrolyze unmethylated cap analog (GpppG) and shows no decapping activity on intact m7GpppG-capped mRNA molecules longer than 25 nucleotides. Does not hydrolyze 7-methylguanosine diphosphate (m7GDP) to m7GMP (PubMed:22985415). May also play a role in the 5'->3 mRNA decay pathway; m7GDP, the downstream product released by the 5'->3' mRNA mediated decapping activity, may be also converted by DCPS to m7GMP (PubMed:14523240). Binds to m7GpppG and strongly to m7GDP. Plays a role in first intron splicing of pre-mRNAs. Inhibits activation-induced cell death.

Drugs associated with DCPS

JCS-1

Target

DCPS

Mechanism

DCPS inhibitors

Active Org.

Yale University

Originator Org.

Yale University

Active Indication

Acute Myeloid Leukemia

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

PF-DcpSi

Target

DCPS

Mechanism

DCPS inhibitors

Active Org.

Pfizer Inc.

Originator Org.

Pfizer Inc.

Active Indication

Spinal Muscular Atrophy

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

D156844

Target

DCPS

Mechanism

DCPS inhibitors

Active Org.

Thomas Jefferson University [+4]

Originator Org.

deCODE chemistry [+4]

Active Indication

Spinal Muscular Atrophy

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with DCPS

100 Translational Medicine associated with DCPS

0 Patents (Medical) associated with DCPS

254

Literatures (Medical) associated with DCPS

01 Dec 2024·Genetic Testing and Molecular Biomarkers

Detection of Genetic Variations in Children with Tetralogy of Fallot Using Whole Exome Sequencing Technology Integrated Bioinformatics Analysis

Article

Author: Ali, Ahmed Faisal ; Shu, Qiang ; Abdullahi, Khalid Mohamoud ; Adan, Mohamed Mohamoud

Background: Tetralogy of Fallot (TOF) is the most common cyanotic heart defect in newborns, with a complex etiology and genetic variation considered to be one of the main pathogenic factors. Identifying genetic variations associated with TOF has important clinical value for understanding its pathogenesis, patient susceptibility, and prognosis of patients with TOF. Therefore, this study aimed to identify potential pathogenic genes of TOF through comprehensive genetic analysis. Materials and Methods: In this study, we employed whole exome sequencing (WES) of the DNA of 47 Chinese children who received surgical TOF treatment at the Children's Hospital of Zhejiang University of Medicine and processed for DNA extraction and quantification of the DNA following WES using the Illumina NovaSeq platform. WES data undergo strict quality control and analysis processes including alignment, postprocessing, variant calling, annotation, and prioritization. Key tools, such as GATK's haplotype calling module and Annotate Variation, were used for variant annotation. In addition, by combining bioinformatics tools such as SIFT, Polyphen2, and Clin Pred, we evaluated the potential impact of nonsynonymous mutations on protein function and referred to relevant literature to support our prediction. Results: Comprehensive data analysis and quality assessment analysis corroborated the data generated from the WES dataset of 47 patients with TOF. Interpreting variants from the perspective of clinical pathogenicity results revealed a novel polymorphism and variant associated with TOF. The identified genetic results revealed evidence for a major contribution of MUTYH, RARB, GFM1, PDZD2, CEP57, DCPS, POMT2, BUB1B, CYP19A1, MAZ, USP10, and TCF3 and provided novel findings for functionally interacting proteins associated with the pathomechanism of TOF. Seven pathogenic variants related to TOF were detected, most of which were previously unreported in this cohort. Conclusions: The genetic variations discovered in this study emphasize the importance of genetic factors in the pathogenesis of TOF, revealing its complex molecular pathways and protein-protein interactions. The study of genetic diversity provides a new perspective for understanding the etiology of TOF and promotes an in-depth exploration of its pathological mechanisms. These findings lay the foundation for subsequent clinical research and the development of treatment strategies.

25 Oct 2024·Medicine

Identification and validation of novel genes related to immune microenvironment in polycystic ovary syndrome

Article

Author: Liu, Liying ; Wang, Haijun ; Ji, Laixi ; Lan, Ying ; Cao, Yuxia ; Zhao, Yuemeng ; Hao, Jianheng

Polycystic ovary syndrome (PCOS) is one of the most complicated chronic inflammatory diseases in women of reproductive age and is one of the primary factors responsible for infertility. There is substantial dispute relating to the pathophysiology of PCOS. Consequently, there is a critical need for further research to identify the factors underlying the pathophysiology of PCOS. Three transcriptome profiles of granulosa cells from patients with PCOS and normal controls were obtained from the gene expression integration database. We also obtained relevant microarrays of granulocytes prepared from PCOS patients and normal controls from the gene expression integration database. Then, we used the R package to perform correlations and identify differences between PCOS and normal controls with regard to immune infiltrating cells and functionality. Subsequently, intersecting genes were identified and risk models were constructed. Finally, the results were validated by enzyme linked immunosorbent assay and real-time PCR. We identified 8 genes related to cuproptosis (SLC31A1, PDHB, PDHA1, DLST, DLD, DLAT, DBT, and ATP7A) and 5 genes related to m7G (SNUPN, NUDT16, GEMIN5, DCPS, and EIF4E3) that were associated with immune infiltration. Furthermore, the expression levels of DLAT (P = .049) and NUDT16 (P = .024) differed significantly between the PCOS patients and normal controls, as revealed by multifactorial analysis. Both DLAT and NUDT16 were negatively correlated with immune cell expression and function and expression levels were significantly lower in the PCOS group. Finally, real-time PCR and enzyme linked immunosorbent assay demonstrated that the expression levels of DLAT and NUDT16 were significantly reduced in the granulosa cells of PCOS patients. In conclusion, our findings shed fresh light on the roles of immune infiltration, cuproptosis, and m7G alternations in PCOS. We also provide a reliable biomarker for the pathological classification of PCOS patients.

21 Aug 2024·ACS Bio & Med Chem Au

Bioproduction Platform to Generate Functionalized Disulfide-Constrained Peptide Analogues

Article

Author: Wu, Hao ; Di Lello, Paola ; Holder, Patrick ; Balana, Aaron T. ; Fuhrmann, Jakob ; Li, Yanjie ; Clarkson, Michael ; Hwang, Sunhee ; Dagdas, Yavuz ; Gao, Xinxin ; Martin, Bryan ; Schroeder, Christina I. ; Miller, Stephen E.

Disulfide-constrained peptides (DCPs) have gained increased attention as a drug modality due to their exceptional stability and combined advantages of large biologics and small molecules. Chemical synthesis, although widely used to produce DCPs, is associated with high cost, both economically and environmentally. To reduce the dependence on solid phase peptide synthesis and the negative environmental footprint associated with it, we present a highly versatile, low-cost, and environmentally friendly bioproduction platform to generate DCPs and their conjugates as well as chemically modified or isotope-labeled DCPs. Using the DCP against the E3 ubiquitin ligase Zinc and Ring Finger 3, MK1-3.6.10, as a model peptide, we have demonstrated the use of bacterial expression, combined with Ser ligation or transglutaminase-mediated XTEN ligation, to produce multivalent MK1-3.6.10 and MK1-3.6.10 with N-terminal functional groups. We have also developed a bioproduction method for the site-specific incorporation of unnatural amino acids into recombinant DCPs by the amber codon suppression system. Lastly, we produced ¹⁵N/¹³C-labeled MK1-3.6.10 with high yield and assessed the performance of a semiautomated resonance assignment workflow that could be used to accelerate binding studies and structural characterization of DCPs. This study provides a proof of concept to generate functionalized DCPs using bioproduction, providing a potential solution to alleviate the reliance on hazardous chemicals, reduce the cost, and expedite the timeline for DCP discovery.

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