University of Rhode Island
Pharmacy
An increasing number of natural and synthetic peptides with the ability to translocate the plasma membrane are being investigated for their application as drug delivery agents. These cell-penetrating peptides (CPP) are recognized by their... more
Abstract Src protein-tyrosine kinase contains a myristoylation motif, a unique region, an Src homology (SH) 3 domain, an SH2 domain, a catalytic domain, and a C-terminal tail. The C-terminal tail contains a Tyr residue, Tyr 527.... more
Fatty acyl-glycol phosphate triester conjugates of 3′-fluoro-2′, 3′-dideoxythymidine (FLT) were prepared in three steps from the reaction of diisopropylphoramidous dichloride with fatty acyl-substituted glycols, followed by a coupling... more
Abstract Protein tyrosine kinases (PTK) are key enzymes of mammalian signal transduction. For the fidelity of signal transduction, each PTK phosphorylates only one or a few proteins on specific Tyr residues. Substrate specificity is... more
Abstract The interaction of a synthetic tetrafluorotyrosyl peptide substrate with the activated tyrosine kinase domain of the insulin receptor was studied by steady-state kinetics and x-ray crystallography. The pH-rate profiles indicate... more
Two polymer-supported reagents for methylphosphorylation and phosphorylation of carbohydrates have been developed. p-Hydroxybenzyl alcohol and β-mercaptoethanol were immobilized on cross-linked divinylbenzene-polystyrene copolymer and... more
Abstract Despite the success of potent reverse transcriptase (RT) inhibitors against human immunodeficiency virus type 1 (HIV-1) in combination regimens, the development of drug resistant RTs constitutes a major hurdle for the long-term... more
Protein kinases play critical roles in signal transduction pathways by transmitting extracellular signals across the cell membrane to distant locations in the cytoplasm and the nucleus. The development of protein kinase inhibitors has... more
Chloromethyl polystyrene resin was reacted with 5-hydroxysalicylaldehyde in the presence of potassium carbonate to afford polymer-bound 2-hydroxybenzaldehyde. Subsequent reduction with borane solution produced polymer-bound... more
Purpose: The objective of this study was to evaluate a dual action prodrug concept wherein an unnatural myristic acid analogue is coupled via an ester moiety to the 5'-position of FLT or AZT. Subsequent intracellular cleavage of the... more
Tripodal peptide analogues were designed on the basis of the phosphotyrosine binding pocket of the Src SH2 domain and assayed for their ability to bind to fluorescein-labeled phosphopeptides. Fluorescence polarization assays showed that a... more
The hitherto unknown (±)-4-methoxydecanoic acid was synthesized in six steps and in 25% overall yield starting from commercially available 4-penten-1-ol. The title compound demonstrated 17-fold higher antifungal activity (MIC= 1.5 mM)... more
Abstract The plasma and tissue disposition of two novel dextran prodrugs of methylprednisolone (MP) containing one (DMP-1) or five (DMP-5) amino acids as linkers were studied in rats. Single 5-mg/kg doses (MP equivalent) of each prodrug... more
Abstract The hitherto unknown 2, 6-hexadecadiynoic acid, 2, 6-nonadecadiynoic acid, and 2, 9-hexadecadiynoic acid were synthesized in two steps and in 11–18% overall yields starting from either 1, 5-hexadiyne or 1, 8-nonadiyne.
Abstract The C-terminal Src kinase (Csk) family of protein tyrosine kinases contains two members: Csk and Csk homologous kinase (Chk). Both phosphorylate and inactivate Src family kinases. Recent reports suggest that the Src homology (SH)... more
4-Thiatetradecanoic acid exhibited weak antifungal activities against Candida albicans (ATCC 60193), Cryptococcus neoformans (ATCC 66031), and Aspergillus niger (ATCC 16404)(MIC= 4.8–12.7 mM). It has been demonstrated that α-methoxylation... more
Abstract Protein kinases are enzymes that covalently modify proteins by attaching phosphate groups (from ATP) to serine, threonine, and/or tyrosine residues. In so doing, the functional properties of the protein kinase's substrates are... more
Abstract Protein tyrosine kinases are key enzymes of mammalian signal transduction. Substrate specificity is a fundamental property that determines the specificity and fidelity of signaling by protein tyrosine kinases. However, how... more
Aminomethyl polystyrene resin was reacted with 4-(5'-formyl-2'-hydroxyphenyl) benzoic acid and 4-(5'-formyl-2'-hydroxyphenyl) phenyl propionic acid, respectively, in the presence of 1-hydroxybenzotriazole and 1, 3-diisopropylcarbodiimide... more