ChemInform Abstract: Molecular Libraries in Liquid Phase via Ugi‐MCR

Ugi, Ivar; Goebel, Matthias; Gruber, Bernhard; Heilingbrunner, Martin; Heiss, Carola; Hoerl, W.; Kern, Oliver; Starnecker, Manfred

doi:10.1002/chin.199709273

Cited by 1 publication

(1 citation statement)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The use of Ugi reaction for chemical library construction is not new: a number of other studies have generated chemical libraries through the multi-component one-pot reaction. 5,6 Nevertheless, it has never been used for constructing a library of nutrient conjugates. Reaction components were chosen mainly from nutrients or their precursors that are often included in multivitamin supplements: 20 fatty acids and 3 vitamins as carboxylic acid components; glucosamine and a vitamin, two monoamines, 4 amino acids, and two biologically active peptides (VPP 7 and carnosine 8,9 ) as amine components, 3 alde-hydes corresponding to glycine, valine, phenylalanine; and ethyl isocyanoacetate to form a glycine ester terminus.…”

Section: Resultsmentioning

confidence: 99%

Nutrient-Based Chemical Library as a Source of Energy Metabolism Modulators

et al. 2019

View full text Add to dashboard Cite

Covalent conjugates of multiple nutrients often exhibit greater biological activities than each individual nutrient and more predictable safety profiles than completely unnatural chemical entities. Here we report the construction and application of a focused chemical library of 308 covalent conjugates of a variety of small-molecule nutrients. Screening of the library with a reporter gene of sterol regulatory element-binding protein (SREBP), a master regulator of mammalian lipogenesis, led to the discovery of a conjugate of docosahexaenoic acid (DHA), glucosamine, and amino acids as an inhibitor of SREBP (molecule 1, DHG). Mechanistic analyses indicate that molecule 1 impairs the SREBP activity by inhibiting glucose transporters and thereby activating AMP-activated protein kinase (AMPK). Oral administration of molecule 1 suppressed the intestinal absorption of glucose in mice. These results suggest that such synthetic libraries of nutrient conjugates serve as a source of novel chemical tools and pharmaceutical seeds that modulate energy metabolism.

show abstract