A series of sterically hindered 0-hydroxy aromatic ketones were synthesized, including benzeae, naphthalene, pbeoanthene and pyrene derivatives. Deuterium isotope effects on the 13C chemical shifts of 2-hydroxy-l-acenaphthone and other sterically hindered, intramolcularly hydrogen-bonded aromatic ketones (OH exchanged) are shown to he M U S U~~. The two-bond isotope effects are very large. Likewise are the istope eff& on C-0, C-1, C-3 a d C-4 carbon resonances and some show unltsual signs. These unusual effects 8re e x p l a i d by a higher degree of twist in the deuterio than the protio compound. Steric isotope effects are also observed on OH chemical shifts of sterically hindered o-hydroxy acetyl aromatic compounds deuteriated at the methyl group. These isotope effeets show non-additivity. For one-bond isotope effects, IA"C ( l a 0), hydrogen bonding leads to a decrease, whereas twisting of the carbonyl group leads to an increase. Two hydrogen bonds to the same acceptor has a reduced cumulative effect. Data for sterically hindered, hydrogen-bonded compounds are found to fall outside the correlation between 6(''O) and 1A13C(180).KEY WORDS NMR NMR Isotope effects on "C chemical shifts Deuterium isotope effects "0 isotope effects Intramolecular hydrogen bonding Steric strain Hydrogen bond strength
The myelin basic protein (MBP) gene is a candidate locus for disease susceptibility in multiple sclerosis (MS). In the present study a part of the tetranucleotide (TGGA)n repeat polymorphism 5’to the MBP gene was examined in 90 Danish MS patients and 106 controls. Lymphocyte DNA was isolated and used in PCR assay. The PCR fragments produced were separated by agarose and acrylamide electrophoresis. Hereby we found three different bandpattems i.e. a homozygote with a 450 bp fragment, a homozygote with a fragment 375 bp and a heterozygote with both bands present. The 450 bp fragment occurred significantly more often among MS than in the control group and the 375 bp fragment was underrepresented among MS than in the control group. The differences between incidence of the three band pattern in the MS and the control group were significant different at 1% level. Our study thus indicate that there is an association between MS and a length polymorphism of the 5’end to the MBP gene in Danish MS patients.
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