RESUMO
Five Boc-protected aminooxy and N-alkylaminooxy amines have been synthesized in 60-95% overall yield using a common synthetic strategy from readily available two- and three-carbon Cbz-protected amino alcohols. The amines can be linked to biomolecules via amide formation and incorporated directly into peptoids via submonomer synthesis. Subsequent deprotection of the aminooxy and N-alkylaminooxy groups enables conjugation with desired target molecules via established chemoselective ligation methods. The range of derivatives synthesized allows different distances to be established between the conjugated molecules.
Assuntos
Aminas/síntese química , Peptoides/química , Aminas/química , Ligantes , Estrutura Molecular , EstereoisomerismoRESUMO
We report a rare case of chondrosarcoma metastatic to the choroid. A 64-year-old male with a history of chondrosarcoma metastatic to the lungs and to the spine presented with blurred vision. A choroidal tumor was found. Fine-needle biopsy confirmed the histologic identity of the tumor as chondrosarcoma. Metastatic spread of chondrosarcoma to the eye is extremely rare. When present, lesions may grow rapidly, and systemic prognosis is poor. Co-management with medical oncology is of utmost importance. This is the third case of chondrosarcoma metastatic to the choroid in the literature and the first with bilateral involvement.
RESUMO
OBJECTIVE: IgG4-related disease is an emerging clinical entity which frequently involves tissue within the orbit. In order to appreciate the implications of IgG4 immunostaining, we analyzed gene expression and the prevalence of IgG4- immunostaining among subjects with orbital inflammatory diseases. METHODS: We organized an international consortium to collect orbital biopsies from 108 subjects including 22 with no known orbital disease, 42 with nonspecific orbital inflammatory disease (NSOI), 26 with thyroid eye disease (TED), 12 with sarcoidosis, and 6 with granulomatosis with polyangiitis (GPA). Lacrimal gland and orbital adipose tissue biopsies were immunostained for IgG4 or IgG secreting plasma cells. RNA transcripts were quantified by Affymetrix arrays. RESULTS: None of the healthy controls or subjects with TED had substantial IgG4 staining. Among the 63 others, the prevalence of significant IgG4-immunostaining ranged from 11 to 39% depending on the definition for significant. IgG4 staining was detectable in the majority of tissues from subjects with GPA and less commonly in tissue from subjects with sarcoidosis or NSOI. The detection of IgG4+ cells correlated with inflammation in the lacrimal gland based on histology. IgG4 staining tissue expressed an increase in transcripts associated with inflammation, especially B cell-related genes. Functional annotation analysis confirmed this. CONCLUSION: IgG4+ plasma cells are common in orbital tissue from patients with sarcoidosis, GPA, or NSOI. Even using the low threshold of 10 IgG4+ cells/high powered field, IgG4 staining correlates with increased inflammation in the lacrimal gland based on histology and gene expression.
Assuntos
Doenças Autoimunes/imunologia , Oftalmopatias/imunologia , Imunoglobulina G/metabolismo , Imuno-Histoquímica/métodos , Órbita/imunologia , Adulto , Idoso , Doenças Autoimunes/metabolismo , Doenças Autoimunes/patologia , Oftalmopatias/metabolismo , Oftalmopatias/patologia , Feminino , Humanos , Aparelho Lacrimal/imunologia , Aparelho Lacrimal/metabolismo , Aparelho Lacrimal/patologia , Masculino , Pessoa de Meia-Idade , Órbita/metabolismo , Órbita/patologiaRESUMO
The chemoselective glycosylation of N-alkylaminooxy side chains with unprotected reducing sugars has proven useful for the synthesis of glycopeptides. Herein, we extend the N-alkylaminooxy strategy to the synthesis of glycopeptoids. A N-methylaminooxy submonomer was efficiently synthesized and incorporated into peptoids. Glycosylation of the peptoids proceeded chemoselectively and site-specifically at the N-methylaminooxy moieties. Employing microwave irradiation significantly increased the degree of glycosylation and shortened the reaction times.