Dataset Information

Glycomimetic affinity-enrichment proteomics identifies partners for a clinically-utilized iminosugar.

ABSTRACT: Widescale evaluation of interacting partners for carbohydrates is an underexploited area. Probing of the 'glyco-interactome' has particular relevance given the lack of direct genetic control of glycoconjugate biosynthesis. Here we design, create and utilize a natural product-derived glycomimetic iminosugar probe in a Glycomimetic Affinity-enrichment Proteomics (glyco-AeP) strategy to elucidate key interactions directly from mammalian tissue. The binding partners discovered here and the associated genomic analysis implicate a subset of chaperone and junctional proteins as important in male fertility. Such repurposing of existing therapeutics thus creates direct routes to probing in vivo function. The success of this strategy suggests a general approach to discovering 'carbohydrate-active' partners in biology.

SUBMITTER: Cruz IN

PROVIDER: S-EPMC6485602 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Glycomimetic affinity-enrichment proteomics identifies partners for a clinically-utilized iminosugar.

Cruz Isa N IN Barry Conor S CS Kramer Holger B HB Chuang C Celeste CC Lloyd Sarah S van der Spoel Aarnoud C AC Platt Frances M FM Yang Min M Davis Benjamin G BG

Chemical science 20130708 9

Widescale evaluation of interacting partners for carbohydrates is an underexploited area. Probing of the 'glyco-interactome' has particular relevance given the lack of direct genetic control of glycoconjugate biosynthesis. Here we design, create and utilize a natural product-derived glycomimetic iminosugar probe in a Glycomimetic Affinity-enrichment Proteomics (glyco-A<sup>e</sup>P) strategy to elucidate key interactions directly from mammalian tissue. The binding partners discovered here and th ...[more]

PMID: 31031905

Similar Datasets

Project description:Detection of human papillomavirus (HPV) in head and neck cancer has therapeutic implications. In situ hybridization and immunohistochemistry for p16 are used by surgical pathologists. We compared the sensitivity and specificity of three popular commercial tests for HPV detection in head and neck squamous cell carcinomas with a 'gold standard' HPV PCR assay. A total of 110 prospectively collected, formalin-fixed tumor specimens were compiled onto tissue microarrays and tested for HPV DNA by in situ hybridization with two probe sets, a biotinylated probe for high-risk (HR) HPV types 16/18 (Dako, CA, USA) and a probe cocktail for 16/18, plus 10 additional HR types (Ventana, AZ, USA). The p16(INK4) expression was also assessed using a Pharmingen immunohistochemistry antibody (BD Biosciences, CA, USA). Tissue microarrays were stained and scored at expert laboratories. HPV DNA was detected by MY09/11-PCR, using Gold AmpliTaq and dot-blot hybridization on matched-fresh frozen specimens in a research laboratory. HPV 16 E6 and E7-RNA expression was also measured using RT-PCR. Test performance was assessed by a receiver operating characteristic analysis. HR-HPV DNA types 16, 18 and 35 were detected by MY-PCR in 28% of tumors, with the majority (97%) testing positive for type 16. Compared with MY-PCR, the sensitivity and specificity for HR-HPV DNA detection with Dako in situ hybridization was 21% (95% confidence interval (CI): 7-42) and 100% (95% CI: 93-100), respectively. Corresponding test results by Ventana in situ hybridization were 59% (95% CI: 39-78) and 58% (95% CI: 45-71), respectively. The p16 immunohistochemistry performed better overall than Dako (P=0.042) and Ventana (P=0.055), with a sensitivity of 52% (95% CI: 32-71) and specificity of 93% (95% CI: 84-98). Compared with a gold standard HPV-PCR assay, HPV detection by in situ hybridization was less accurate for head and neck squamous cell carcinoma on tissue microarrays than p16 immunohistochemistry. Further testing is warranted before these assays should be recommended for clinical HPV detection.

Dataset Information

Glycomimetic affinity-enrichment proteomics identifies partners for a clinically-utilized iminosugar.

Publications

Glycomimetic affinity-enrichment proteomics identifies partners for a clinically-utilized iminosugar.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets