Synthesis of UDP-4-deoxy-4-fluoroglucose and UDP-4-deoxy-4-fluorogalactose and their Interactions with Enzymes of Nucleotide Sugar Metabolism

Chapeau, Marie-Christine; Frey, Perry A.

doi:10.1021/jo00102a024

Cited by 44 publications

(30 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, the fluorinated compound, [ 36 Phe( p ‐F)]‐PYY3‐36, both increased Y1/Y2 receptor selectivity and maintained a high affinity to the Y2 receptor (Figure 1 and Table 3, peptide 3 ). Hydroxyl and fluorine share several properties, in particular polarity 40, 41. Fluorine is not a sterically demanding substituent, given its small van der Waals radius (1.35 Å) which resembles the one of hydrogen (1.20 Å) 42.…”

Section: Resultsmentioning

confidence: 99%

Modifying the conserved C‐terminal tyrosine of the peptide hormone PYY3‐36 to improve Y2 receptor selectivity

Pedersen

Holst

Vrang³

et al. 2009

Journal of Peptide Science

View full text Add to dashboard Cite

The Y2 selective PYY derived peptide PYY3-36 was recently shown to play a role in appetite regulation. Novel PYY3-36 analogs with high selectivity for the Y2 receptor could be potential drug candidates for the treatment of obesity. The C-terminal pentapeptide segment of PYY3-36 is believed to bind to the Y receptors. Tyr-36 is highly conserved across species and only few successful modifications of Tyr-36 have been documented. PYY3-36 analogs were prepared using solid-phase peptide chemistry and tested for binding to the Y1, Y2 and Y4 receptor subtypes by radioligand displacement assay. The Y2 receptor agonists with the best affinity and selectivity were further investigated for activity towards the Y1 and Y2 receptor subtypes. Unexpectedly, modifications of Tyr-36 were well-tolerated, and the analogs of PYY3-36 in which the Tyr-36 hydroxyl group was substituted with a halogen or an amino group were particularly well tolerated and yielded an improved selectivity and approximately equipotent affinity to the Y2 receptor. These modifications could be used to design new potential drug candidates for the treatment of obesity.

show abstract

Section: Resultsmentioning

confidence: 99%

Modifying the conserved C‐terminal tyrosine of the peptide hormone PYY3‐36 to improve Y2 receptor selectivity

Pedersen

Holst

Vrang³

et al. 2009

Journal of Peptide Science

View full text Add to dashboard Cite

show abstract

“…It is also well known that organofluorine molecules have enormous applications as drugs, agro chemicals, biomaterials and also in molecular imaging 28,29 . [34][35][36][37][38] In spite of the fact that fluorine containing organic molecules have great importance in number of fields, the study of intramolecular HB involving organic fluorine is limited owing to the fact it hardly ever accepts intramolecular HB 39-43 44, 45 . In bio-inorganic and medicinal chemistry, the formation of intermolecular X-H … F-C (X=O, N) hydrogen bridges is significantly important because of the binding nature of the fluorinated compounds to enzyme active sites.…”

Section: Introductionmentioning

confidence: 99%

Intramolecular hydrogen bonds involving organic fluorine in the derivatives of hydrazides: an NMR investigation substantiated by DFT based theoretical calculations

Mishra

Suryaprakash

2015

Phys. Chem. Chem. Phys.

View full text Add to dashboard Cite

The rare examples of intramolecular hydrogen bonds (HB) of the type the N-H∙∙∙F-C, detected in a low polarity solvent in the derivatives of hydrazides, by utilizing one and two-dimensional solution state multinuclear NMR techniques, are reported. The observation of through-space couplings, such as, (1h)JFH, and (1h)JFN, provides direct evidence for the existence of intra-molecular HB. Solvent induced perturbations and the variable temperature NMR experiments unambiguously establish the presence of intramolecular HB. The existence of multiple conformers in some of the investigated molecules is also revealed by two dimensional HOESY and (15)N-(1)H HSQC experiments. The (1)H DOSY experimental results discard any possibility of self or cross dimerization of the molecules. The derived NMR experimental results are further substantiated by Density Function Theory (DFT) based Non Covalent Interaction (NCI), and Quantum Theory of Atom in Molecule (QTAIM) calculations. The NCI calculations served as a very sensitive tool for detection of non-covalent interactions and also confirm the presence of bifurcated HBs.

show abstract

“…Fluorine‐substituted analogs of naturally occurring and biologically active organic compounds are widely studied 1–18. It has already become a common practice in bioorganic chemistry to replace a hydroxyl group for a fluorine to generate a fluorinated enzyme substrate or inhibitor in a given enzymatic process 3–7.…”

Section: Introductionmentioning

confidence: 99%

When, in the context of drug design, can a fluorine atom successfully substitute a hydroxyl group?

Hoffmann

Rychlewski

2002

Int J of Quantum Chemistry

View full text Add to dashboard Cite

ABSTRACT:In this article, we deal with the question of whether a fluorine atom can substitute a hydroxyl group in such a way that will lead to a compound showing a desired biologic activity, that is, a potential new drug. It is obvious that a fluorine atom differs from a hydroxyl group, as it cannot donate hydrogen bonds. However, it can accept them. Moreover, both fluorine and oxygen are of similar size and are the most electronegative elements. Therefore, a fluorine atom is thought to be a good substitute for a hydroxyl group. However, it was shown that for conformationally labile aliphatic compounds a replacement of a hydroxyl by a fluorine increases conformational diversity, so the fluorinecontaining aliphatic molecules are present in equilibrium at room temperature as a mixture of several different conformers. In contrast, for cyclic compounds the substitution of an OH group by an F atom does not much change shape and electrostatic potential around corresponding conformers. Moreover, these compounds are present in equilibrium at room temperature in aqueous solution as a mixture of the same most favored structures.

show abstract

Synthesis of UDP-4-deoxy-4-fluoroglucose and UDP-4-deoxy-4-fluorogalactose and their Interactions with Enzymes of Nucleotide Sugar Metabolism

Cited by 44 publications

References 0 publications

Modifying the conserved C‐terminal tyrosine of the peptide hormone PYY3‐36 to improve Y2 receptor selectivity

Modifying the conserved C‐terminal tyrosine of the peptide hormone PYY3‐36 to improve Y2 receptor selectivity

Intramolecular hydrogen bonds involving organic fluorine in the derivatives of hydrazides: an NMR investigation substantiated by DFT based theoretical calculations

When, in the context of drug design, can a fluorine atom successfully substitute a hydroxyl group?

Contact Info

Product

Resources

About