Ralph Paulini

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The past few decades of molecular recognition studies have greatly enhanced our knowledge on apolar, ion-dipole, and hydrogen-bonding interactions. However, much less attention has been given to the role that multipolar interactions, in particular those with orthogonal dipolar alignment, play in organizing a crystal lattice or stabilizing complexes(More)
Inhibition of the enzyme catechol O-methyltransferase offers a therapeutic handle to regulate the catabolism of catecholamine neurotransmitters, providing valuable assistance in the treatment of CNS disorders such as Parkinson's disease. A series of ribose-modified bisubstrate inhibitors of COMT featuring 2'-deoxy-, 3'-deoxy-, 2'-aminodeoxy-3'-deoxy-, and(More)
The biological activity of catechol neurotransmitters such as dopamine in the synapse is modulated by transporters and enzymes. Catechol-O-methyltransferase (COMT; EC 2.1.1.6) inactivates neurotransmitters by catalyzing the transfer of a methyl group from S-adenosylmethionine to catechols in the presence of Mg²⁺. This pathway also inactivates L-DOPA, the(More)
L-Dopa, the standard therapeutic for Parkinson's disease, is inactivated by the enzyme catechol-O-methyltransferase (COMT). COMT catalyzes the transfer of an activated methyl group from S-adenosylmethionine (SAM) to its catechol substrates, such as L-dopa, in the presence of magnesium ions. The molecular recognition properties of the SAM-binding site of(More)
A series of 5'-linked stilbene-DNA conjugates with different substituents in the distal aromatic ring of the stilbene was prepared, and the effect of the modifications on duplex stability was determined via UV-melting curves. A trimethoxystilbene derivative as a 5'-substituent increases duplex melting points by up to 12.2 degrees C per modification. With(More)
Hexacyclic congeners 3 and 4 of palau'amine, which incorporate both guanidine functional groups and have the cis configuration of the azabicyclo[3.3.0]octane core, are prepared in 14 steps from cycloadduct 6. Synthetic access to these analogues allows the first direct comparison of NMR data for hexacyclic diguanidine structures having the originally(More)
The exposed terminal base pairs of DNA duplexes are nonclassical binding sites for small molecules. Instead, small molecules usually prefer intercalation or minor groove binding. Here we report the solution structure of the DNA duplex (TMS-TGCGCA)(2), where TMS denotes trimethoxystilbene carboxamides that are 5'-tethered to the DNA. The stilbenes, for which(More)
A convergent, enantioselective total synthesis of (+)-guanacastepene N was developed that features a 7-endo Heck cyclization as the key step. In the course of this synthesis, short syntheses of the enantiomerically pure cyclopentenone and cyclohexene building blocks 5 and 6, which constitute A and C ring fragments of guanacastepene N, were developed. These(More)